Time-related aortic inflammatory response, as assessed with 18F-FDG PET/CT, in patients hospitalized with severely or critical COVID-19: the COVAIR study.

AIM: Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). Fluorine 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of aortic inflammation and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend in patients with COVID-19. METHODS: Between November 2020 and May 2021, in this pilot, case-control study, we recruited 20 patients with severe or critical COVID-19 (mean age of 59 ± 12 years), while 10 age and sex-matched individuals served as the control group. Aortic inflammation was assessed by measuring 18F-FDG uptake in PET/CT performed 20-120 days post-admission. Global aortic target to background ratio (GLA-TBR) was calculated as the sum of TBRs of ascending and descending aorta, aortic arch, and abdominal aorta divided by 4. Index aortic segment TBR (IAS-TBR) was designated as the aortic segment with the highest TBR. RESULTS: There was no significant difference in aortic 18F-FDG PET/CT uptake between patients and controls (GLA-TBR: 1.46 [1.40-1.57] vs. 1.43 [1.32-1.70], respectively, P = 0.422 and IAS-TBR: 1.60 [1.50-1.67] vs. 1.50 [1.42-1.61], respectively, P = 0.155). There was a moderate correlation between aortic TBR values (both GLA and IAS) and time distance from admission to 18F-FDG PET-CT scan (Spearman's rho = - 0.528, P = 0.017 and Spearman's rho = - 0.480, p = 0.032, respectively). Patients who were scanned less than or equal to 60 days from admission (n = 11) had significantly higher GLA-TBR values compared to patients that were examined more than 60 days post-admission (GLA-TBR: 1.53 [1.42-1.60] vs. 1.40 [1.33-1.45], respectively, P = 0.016 and IAS-TBR: 1.64 [1.51-1.74] vs. 1.52 [1.46-1.60], respectively, P = 0.038). There was a significant difference in IAS- TBR between patients scanned ≤ 60 days and controls (1.64 [1.51-1.74] vs. 1.50 [1.41-1.61], P = 0.036). CONCLUSION: This is the first study suggesting that aortic inflammation, as assessed by 18F-FDG PET/CT imaging, is increased in the early post COVID phase in patients with severe or critical COVID-19 and largely resolves over time. Our findings may have important implications for the understanding of the course of the disease and for improving our preventive and therapeutic strategies.

Positron emission tomography after response to rituximab-CHOP in primary mediastinal large B-cell lymphoma: impact on outcomes and radiotherapy strategies.

End-of-treatment (EoT) PET/CT is used as a guide to omit radiotherapy (RT) patients with primary mediastinal large B-cell lymphoma (PMBCL). We present the mature and extended results of a retrospective study evaluating the prognostic significance of EoT-PET/CT after adequate response to R-CHOP. Among 231 consecutive PMLBCL patients, 182 underwent EoT-PET/CT and were evaluated according to the Deauville 5-point scale (D5PS) criteria. Freedom from progression (FFP) was measured from the time of PET/CT examination. Among 182 patients, 72 (40%) had D5PS score 1 (D5PSS-1), 33 (18%) had 2, 28 (15%) had 3, 29 (16%) had 4, and 20 (11%) had 5. The 5-year FFP was 97, 94, 92, 82, and 44% for D5PSS-1, D5PSS-2, D5PSS-3, D5PSS-4, and D5PSS-5, respectively. Among 105 patients with unequivocally negative PET/CT (D5PSS-1/D5PSS-2), 49 (47%) received RT (median dose 3420 cGy) and 56 (53%) did not with relapses in 0/49 vs. 4/56 patients (2 mediastinum and 2 isolated CNS relapses).The 5-year FFP for those who received RT or not was 100% versus 96%, when isolated CNS relapses were censored (p = 0.159). Among D5PSS-3 patients (27/28 irradiated-median dose 3600 cGy), the 5-year FFP was 92%. The 5-year FFP for D5PSS-4 and D5PSS-5 was 82 and 44%; 44/49 patients received RT (median dose 4000 and 4400 cGy for D5PSS-4 and D5PSS-5). Our study supports the omission of RT in a sizeable fraction of PET/CT-negative patients and definitely discourages salvage chemotherapy and ASCT in patients with PMLBCL who conventionally respond to R-CHOP, solely based on PET/CT positivity in the absence of documented progressive or multifocal disease. The persistence of positive PET/CT with D5PSS < 5 after consolidative RT should not trigger the initiation of further salvage chemotherapy in the absence of conventionally defined PD.

[Comparative evaluation of Iterative and FORE-Iterative reconstruction algorithms for PET/CT].

In this study, the properties of the reconstruction algorithm Iterative in comparison with the FORE-Iterative using 18F-FDG PET/CT data were evaluated. The study was conducted in the Department of Nuclear Medicine of Evangelismos Athens General Hospital, in which data from 9 patients were collected and reconstructed with both algorithms, Iterative and FORE-Iterative. For each patient, the image quality was assessed using parameters such as SUVmax, SUVpeak, SUVmean, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR). Regions of interest were defined based on medical expertise focusing on the tumor areas. Based on the results of this study, images reconstructed with Iterative algorithm have better image quality compared to the images reconstructed with FORE-Iterative algorithm, considering that this particular method improves SNR and CNR. Using the Iterative algorithm, the image becomes sharper due to reduced noise resulting in safer clinical observations, and as a result a more accurate diagnosis.

CT guided mediastinal biopsy facilitated by PET/CT imaging: Our experience.

The purpose of this retrospective study is to assess the efficacy of mediastinal tumor biopsies guided by computed tomography (CT) and facilitated by positron emission tomography (PET)/CT in our hospital. We also wanted to prove the use of PET/CT in performing such biopsies. Fifty-two patients were biopsied under CT guidance with PET/CT visual co-registration (35) and facilitated PET/CT registration (17). In 49 patients, a diagnosis from the guided biopsy performed was successful and in 3 patients the results were inconclusive. Our results allow us to claim that the accuracy of CT-guided mediastinal biopsies facilitated by PET/CT allow for precise localization of higher tumor metabolism, potentially reduce the number of needle passes needed and increase the success rate of the procedure.

[Cost analysis and evaluation of a PET/CT system-department in a public Greek hospital].

OBJECTIVE: Positron emission tomography/computed tomography (PET/CT) is an imaging technology that has experienced rapid development in recent years. The aim of this paper was to present the financial viability of a PET/CT department in a public hospital of Athens, Greece. This study performs a detailed financial analysis of the operating revenues and expenses of the department for the years 2007-2017. SUBJECTS AND METHODS: For each year considered, detailed analysis of incomes and expenses has been performed. During a normal working day 15 scans are acquired by the PET/CT department. Over the 11 years of operation, 22.035 scans had been performed in total. The turnover for the examined period reached €40.395.275 is this cumulative revenue over the 11 years. RESULTS: The following 6 evaluation and decision-making methods are presented: a) Net present value of the investment 2.245.251€ (factor ß beta 0,6923), b) Internal rate of return was estimated 34,89%, c) The payback period is achieved by 2011, d) The profitability index is 2,10, e) Average rate of return or accounting rate of return is 27,20%, and f) Return On Investment is estimated 299,25%. CONCLUSION: Even if we have to consider that it is not proper to evaluate with financial terms health, it is concluded through the present study that the investment for settling and operating the under-examination PET/CT unit of the present public hospital was financially profitable.

More advantages in detecting bone and soft tissue metastases from prostate cancer using 18F-PSMA PET/CT.

Prostate cancer (PCa) is the most common solid cancer affecting men worldwide. Serum prostate-specific antigen (PSA) is at present the most commonly used biomarker for PCa screening, as well as a reliable marker of disease recurrence after initial treatment. Bone metastases (BM) are present in advanced stages of the disease. Imaging of BM is important not only for localization and characterization, but also to evaluate their size and number, as well as to follow-up the disease during and after therapy. Bone metastases formation is triggered by cancer initiating cells in the bone marrow and is facilitated by the release of several growth factors. Although BM from PCa are very heterogenic, the majority of them are described as "osteoblastic", while pure "osteolytic" metastases are very rare. The PSA levels, along with other parameters, may determine the risk of having BM. A classification report, which is currently in use, divides patients into three categories according to the risk of having BM: low risk (PSA<10ng/mL, clinical stage T1-T2a, Gleason Score ≤6), intermediate risk (PSA 10.1-20ng/mL, clinical stage T2b-T2c, Gleason Score=7) and high risk (PSA>20ng/mL, clinical stage T3a or higher, or Gleason Score ≥8). Even though PSA remains the only biomarker of this disease in clinical practice, it is not always analogue with the severity of the disease and should be evaluated along with the clinical and diagnostic imaging findings. Detection of BM is not always easy, as there may be unexpected sites and occult metastases. The clinical importance of revealing BM in patients with PCa is to determine the overall survival of the patients and their quality of life, as BM may lead to high morbidity and mortality. There are many options of treating BM, such as chemotherapy, immunotherapy, external beam radiotherapy, bone modifying agents and recently prostate-specific membrane antigen (PSMA) targeted therapies. Another potential therapy is radioguided surgery, in patients with occult and/or focally recurrent PCa. Such a single occult metastasis causing very high levels of PSA has been presented using technetium-99m (99m Tc) labeled PSMA imaging. Diagnosis and staging of PCa mostly relies on the morphology of imaging, using computerized tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/CT (PET/CT) using fluorine-18-fluorodeoxyglucose (18 F-FDG). The radiopharmaceuticals used in Nuclear Medicine for BM in PCa are: a) those that target lesions, such as 99m Tc-phosphonates, 18 F-sodium fluoride (18 F-NaF) and b) those that target the cancer cells, such as 18 F or carbon-11 (11 C)-choline, 18 F-FDG and 18 F or gallium-68 (68 Ga)-PSMA. Bone scan with 99mTc-phosphonates is widely used for the evaluation of bone metabolism in patients with PCa. It is a low cost, widely available radiopharmaceutical having the advantage of a whole body evaluation. Planar and single photon emission tomography (SPET) may also be applied. The sensitivity of the whole body scan (WBS) ranges from 75%-95%, while the specificity is lower, ranging from 60%-75% due to false positive findings in benign conditions (arthritis, inflammation etc) who also have increased bone metabolism. Sensitivity and specificity however, perform better (96% and 94% respectively) when SPET and SPET/CT techniques are applied. Of course, bone marrow metastases cannot be detected in a WBS. The PSA marker is used to predict the pre-test probability of BM and in case of a bone scan several retrospective analyses showed that PSA levels <20ng/mL can exclude with high probability a positive WBS, with a high negative predictive value (almost 99%). The European Association of Urology (EAU) guidelines state that a bone scan can be omitted in patients with PSA levels <20ng/mL and with a Gleason Score ≤7. Imaging with 18 F-NaF PET/CT is characterized by high and rapid bone uptake, minimal serum protein binding and rapid blood clearance which lead to a fast and high target to background ratio with a short acquisition time (30 minutes). Sensitivity and specificity for the detection of BM in high risk PCa patients is almost 100%. The main advantages provided by 18 F-NaF PET/CT are the better imaging quality along with a whole body acquisition and the fusion technique. Fluorine-18-choline and 11 C-choline PET/CT came to practice lately, reflecting the cell membrane metabolism. Choline is an essential component of phospholipids and is trapped in the cells after a phosphorylation by a choline kinase. The sensitivity and specificity of 18 F-choline PET/CT for detecting BM in patients with PCa is reported to be 79% and 97% respectively. However, the performance of choline PET/CT seems to be dependent of the levels of the PSA, in cases of biochemical recurrence and reaches about 75%% in those PCa patients with PSA levels >3ng/mL, with a poor performance when the PSA level is low. Fluorine-18-FDG is the most commonly used radiotracer in PET/CT, however has a little value in staging and restaging of PCa. Because of its low sensitivity 18 F-FDG is trapped in cancer cells through the activation of the glycolytic pathways and in case of BM is an index of increased glucose metabolism in PCa cells rather than in bone lesion per se. Osteolytic lesions show more increased metabolic activity than the osteoblastic lesions and are better revealed with 18F-FDG. Therefore, 18 F-FDG PET/CT is suggested to be performed only in selected patients with PCa, those with most aggressive tumors and high Gleason score. Fluorine-18-PSMA PET/CT The need of a more sensitive and specific agent has been evident. Prostate specific monoclonal antibody (PSMA) is a folate hydrolase cell surface glycoprotein. It is mainly expressed in four tissues of the body, including prostate epithelium, the proximal tubules of the kidney, the jejunal brush border of the small intestine and ganglia of the nervous system. So consequently may in some cases be expressed in cancers other than PCa and also in benign processes. It is localized in the cytoplasm and the apical side of the prostate epithelium that lines prostatic ducts. In case of malignant transformation, PSMA is transferred from the cytoplasm to the luminal surface of the prostatic ducts and thus becomes membrane bound. It has a unique three-parts structure, an external portion, a transmembrane portion and an internal-cytoplasmatic portion. Prostate specific monoclonal antibody is also upregulated and thus overexpressed in most PCa, but weakly expressed in normal prostatic tissue. Imaging by PSMA PET/CT has been shown to detect sites of disease recurrence at lower PSA levels than conventional imaging. The PSMA overexpression is even present when the cell becomes castrate-resistant and that is the reason why it is the most favorable target for PET imaging. Prostate cancer expresses 100 to 1000 times more PSMA than normal tissue and is increasing even more in higher grade tumors as well as in increased castrate resistance. Therefore, PSMA represents an excellent target for both diagnostic imaging and endoradiotherapy of PCa. For diagnostic purposes PSMA ligands, mainly small-molecule inhibitors, are most commonly labeled either with 68 Ga or 18 F. The 18 F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18 F-fluoronicotinamido) butanamido) methyl phenyl)-3- (naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane- 10,14,16-tricarboxylic acid)) seems to be more favorable among other 18 F-PSMA ligands candidate compounds because it demonstrates high labeling yields, better tumor uptake and non-urinary background clearance. On the contrary, 68 Ga-PSMA is rapidly excreted via the urinary tract resulting in intense accumulation in the bladder, thus, obscuring the prostate. Compared to 68 Ga, 18 F has many advantages such as it is produced in larger amounts, it has a longer half life and a higher physical spatial resolution. The short half-life of 68 Ga relative to 18 F (68 vs. 110 min) makes 68 Ga-PSMA inconvenient for longer transport, so that it is almost mandatory to use local gallium generators, which have a higher cost and lower yields at the end of their first half-life. Each generator provides only one or two elutions per day and it requires separate syntheses at different times of the day in a local radiopharmacy. Furthermore, the resolution of 68 Ga-labeled tracers is physically limited because of positron range effects. In contrast, 18 F labels avoid these intrinsic difficulties and can be produced at high yields in central cyclotrons. Fluorine-18-PSMA-1007 has been recently used by us in the Nuclear Medicine Department of "Evangelismos" general hospital of Athens and our experience so far showed favorable results, with high image resolution acquisitions and lesions which showed PSMA avidity. Fluorine-18-PSMA-1007 PET/CT imaging was carried out with a dual phase protocol, consisting of two separate scans. One (early scan) at 60min post injection starting from the diaphragm to the middle of the thighs and the late scan at 180min from the dome of the skull to the knee joints. Patients were asked to urine before the examination. Images were acquired with a scan time of 3min per bed position on a General Electric PET/CT system and the image reconstruction was performed by the standard software method provided by the manufacturer. A low dose CT scan, without a contrast agent, was performed before the PET scan in order to be used for the attenuation correction. Administered activities were calculated based on the department's protocols with a suggested injected activity of 4MBq/kg. Any areas of focally increased radiotracer uptake, at both the early and late PET scans, were considered as abnormal, despite the presence or absence of morphological changes of the CT scan. The normal distribution of the radiotracer was taken underconsideration, which includes mainly the liver and the gallbladder, as it has hepatobiliary clearance rather than renal, the spleen, the pancreas, the submandibular, sublingual, lacrimal and parotid glands, the kidneys, the urinary bladder and the small intestine. The maximum standardized uptake value (SUVmax) was calculated for each lesion. A typical case of a 78 years man with PCa having PSA 7,3ng/mL and also having Paget's disease was tested by the above procedure for initial staging. The 18 F-PSMA-1007 PET/CT imaging revealed diffusely increased radiotracer uptake in the bones of the pelvis with a SUVmax 9. The CT imaging of the pelvis was consistent with Paget's disease, with diffuse mixed osteosclerotic and osteolytic lesions, accompanied with bone expansion. The primary PCa was also revealed with focally increased radiotracer uptake in the left prostatic lobe with a SUVmax 19, as well as a second small focus of pathologically increased PSMA uptake in the right prostatic lobe with a SUVmax 23. Another patient 79 years old, with PCa was studied with 18 F-choline PET/CT which showed diffuse bone metastasis in the pelvis. He had PSA level, 412ng/mL. The 18 F-PSMA-1007 PET/CT imaging showed multiple foci of increased radiotracer uptake throughout the whole skeleton, including the skull, both humerus and femoral bones with indicative SUVmax 26. Computed tomography showed rather similar BM. There were also lymph nodes metastases at the left internal mammary chain as well as the left inguinal areas, with a SUVmax 25. The first case indicated that 18 F-PSMA PET/CT could easily differentiate PCa BM from Paget's disease, however benign conditions such as Paget's disease may also show PSMA uptake and the second case that 18 F-PSMA PET/CT scan was more sensitive than the 18 F-choline PET/CT scan, with high quality images. According to other authors the SUVmax value of BM in PCa was 16.57±23.59 using the 18 F-PSMA PET/CT scan. This imaging modality in accordance to other authors is better than 68 Ga-labelled PSMA-ligands and can better differentiate BM from healing fractures. Very recently a novel PET radiopharmaceutical has been approved both in USA and Europe: 18 F-fluciclovine (trans-1-amino-3-[18 F] fluoro-cyclobutane carboxylic acid). Fluorine-18-fluciclovine is a synthetic amino acid that is transported by multiple sodium-dependent and sodium-independent channels found to be upregulated in PCa cells. The main indication of use includes the detection and localization of PCa recurrence in patients with a rising PSA following prior therapy. The main advantages of 18 F-fluciclovine are the low urinary excretion, which allows for better evaluation of prostate bed and the low uptake in inflammatory cells (e.g. macrophages). There are no studies in the literature comparing 18 F-PSMA to 18 F-fluciclovine, however two studies comparing 18 F-fluciclovine to 68 Ga-PSMA, showed better performance for 68 Ga-PSMA in PCa patients with biochemical recurrence. So, 18 F-PSMA-1007 PET/CT imaging seems to be very promising in staging and restaging patients with PCa, especially when biochemical relapse is under consideration. Although it seems to perform better than other imaging modalities like bone scan, 18 F-FDG PET/CT or 18 F-choline PET/CT, its high cost and low availability must be considered. Further large studies need to be conducted in order to evaluate the accuracy and the predictive values of this method, emphasizing on bone metastases.

Anatomical and Functional Changes in the Coexistence of Vitreomacular Traction and Epiretinal Membrane: A Spectral-Domain Optical Coherence Tomography Study.

PURPOSE: The purpose of this study was to evaluate the anatomical and functional findings in patients with vitreomacular traction (VMT) combined with epiretinal membrane (ERM) in the same eye. METHODS: In this retrospective, cross-sectional study, we studied 65 patients with VMT and ERM. In 36 of them, ERM/VMT had a 'unified' appearance (group Ι) but in 29, VMT and ERM coexisted without an interrelationship (group ΙΙ). All patients were examined with spectral-domain optical coherence tomography (SD-OCT). We recorded the macular thickness, the presence, type and location of macular edema, the horizontal diameter of VMT, ellipsoid zone/external limiting membrane (EZ/ELM) status, the vitreofoveal angle of VMT nasally and temporally and the best corrected visual acuity (BCVA). RESULTS: Group Ι presented with increased macular thickness, a broader adhesion diameter, extensive EZ/ELM defect and decreased BCVA compared to those where VMT and ERM were not intercorrelated. In group I ('unified' VMT and ERM), cystoid macular edema was found at a greater percentage (41.7%), while in patients where the 2 entities were not intercorrelated, diffuse macular edema was more evident (69%). There was no statistically significant difference between the 2 groups in the vitreofoveal angle temporally and nasally. CONCLUSIONS: Macular thickness, type of macular edema, adhesion diameter, the extent of the EZ/ELM defect and BCVA appeared different in cases where VMT and ERM were unified compared to cases where ERM and VMT coexisted but were not intercorrelated.

Real-life experience after intravitreal ocriplasmin for vitreomacular traction and macular hole: a spectral-domain optical coherence tomography prospective study.

PURPOSE: To evaluate prospectively the anatomical and functional results after ocriplasmin injection in patients with vitreomacular traction (VMT), or macular hole (MH) combined with VMT, providing the real-life experience of three centers, using spectral domain-optical coherence tomography (SD-OCT). METHODS: Twenty-four patients with VMT (17 with VMT alone and 7 with an MH combined with VMT) were treated with a single ocriplasmin injection and followed-up prospectively at baseline, day 1, 7, 28 and the last examination of the follow-up for each patient (range: 30-127 days). Best-corrected visual acuity (BCVA) and SD-OCT were performed for patient assessment, while various adverse events were recorded and analysed. At baseline, univariate analysis was also performed to examine the potential predictive factors for VMT release. RESULTS: 66.7 % of patients presented VMT release at the end of the follow-up, while 28.6 % exhibited MH closure. Baseline positive predictive factors for VMT release were young age, being female, phakic lens status, increased vitreofoveal angle, V-shaped and loose vitreomacular adhesion, small adhesion area, thin vitreous strands at the adhesion site and absence of an epiretinal membrane. Four new cases of ellipsoid line changes and subretinal fluid development became evident at day 7 compared to baseline. Lamellar macular hole (LMH) in four cases was first noticed at day 28 post injection. Formation of cystoid macular edema (CME) was noticed in three new cases at day 28 compared to baseline. CONCLUSIONS: Our study demonstrated a VMT release rate of 66.7 %. Apart from the known baseline factors that influence VMT release after ocriplasmin injection, the size of the vitreofoveal angle, a V-shaped and loose vitreomacular adhesion, a small adhesion area, and thin vitreous strands at the adhesion site, could additionally affect the outcome of VMT release. In addition, we studied when VMT release and concomitant events occur and for how long the induced complications lasted.

Complications of intravitreal ocriplasmin for vitreomacular traction and macular hole: a prospective spectral-domain optical coherence tomography study.

OBJECTIVE: The purpose of this study was to evaluate the safety of intravitreal ocriplasmin prospectively, reporting potential complications in patients with vitreomacular traction (VMT) alone or associated with macular hole (MH). MATERIALS AND METHODS: Participants in this prospective, multicenter study, were 24 patients with VMT (17 with VMT alone and seven with MH combined with VMT). All patients were treated with a single ocriplasmin injection and followed-up prospectively at baseline, day 7, 28 and the last examination of the follow-up for each patient (mean ± SD: 64.2 ± 24.4 d, range: 40-145 d). Best-corrected visual acuity (BCVA) was assessed, and spectral-domain optical coherence tomography was performed at each visit while the percentage of resolution of VMT and the association with various potential adverse events were recorded and analyzed. RESULTS: 66.7% of patients presented VMT release at the end of the follow-up, while 28.6% exhibited MH closure. Severe adverse events, such as enlargement of preexisting MH and formation of lamellar MH, were observed in one and four cases, respectively and remained till the end of the follow-up. Moderate adverse events, such as ellipsoid zone disruption and subretinal fluid development, became evident seven days after injection, in four cases. Formation of cystoid macular edema (CME), not evident at baseline, was noticed in three cases at day 28 after injection. Mild adverse events, like vitreous floaters, photopsias, eye pain and foreign body sensation, were noticed at day 7 and resolved till the end of the follow-up. CONCLUSIONS: Mild and moderate adverse events occurred mainly during the first week of the follow-up, while severe adverse events, such as the lamellar MH formation and CME at day 28 post injection were seen.

Evolution of vitreomacular adhesion to acute vitreofoveal separation with special emphasis on a traction-induced foveal pathology. A prospective study of spectral-domain optical coherence tomography.

PURPOSE: To investigate the evolution of vitreomacular adhesion (VMA) to acute vitreofoveal separation with particular emphasis on cases involving the underlying fovea. METHODS: In this observational case series, of 192 cases in the VMA stage, 51 progressed to acute vitreofoveal separation; this subgroup was divided into those with normal separation (Group I) and those with co-existing macular findings (Group II). All patients were examined using spectral domain-optical coherence tomography (SD-OCT) at regular three-month intervals. We recorded the best-corrected visual acuity (BCVA), the vitreomacular angle of the VMA (nasally and temporally), the horizontal diameter of the VMA, the macular thickness, the integrity of the photoreceptor layer and of the external limiting membrane. The Amsler grid test was used in the intermediate examinations in cases where patients developed symptoms. RESULTS: Out of the 51 cases in the VMA stage, 45 (88.2%) progressed to normal spontaneous vitreofoveal separation, while six (11.8%) developed findings of the fovea, such as macular thinning (two cases), an anomalous foveal contour (two cases), a macular tissue defect (one case) and vitreous separation from only the temporal side of the VMA in one case. Foveal findings were the same during the follow-up period in all but one case in which improvement was noted. Differences in BCVA between baseline measurements, those made immediately after vitreofoveal separation, and those made during final examination were not statistically significant. For the whole sample of our study (51 cases), the mean observation time at the VMA stage was 21.8 ±10.6 months, while the mean follow-up time after vitreofoveal separation was 9.7 ±4.9 months. In cases that developed incidents from the fovea, the mean observation time from the baseline to the last examination before vitreofoveal separation was 16.5 ±11.2 months and the mean follow-up time from the diagnosis of vitreofoveal separation to the final examination was 8.5 ±4.4 months. CONCLUSIONS: VMA, excepting its progression to vitreomacular traction or spontaneous release, in a subset of patients can also cause findings associated with the fovea, concomitantly with vitreofoveal separation. Vitreofoveal separation can induce unilateral anatomic distortion of the fovea accompanied by symptoms, such as metamorphopsia or micropsia.

Impact of early vs late postoperative radioiodine remnant ablation on final outcome in patients with low-risk well-differentiated thyroid cancer.

OBJECTIVE: Postoperative radioiodine remnant ablation (RRA) represents an adjunctive therapeutic modality in patients with differentiated thyroid cancer (DTC). The impact of late vs early RRA on the outcome of DTC is currently unclear. The aim of the study was to evaluate the outcome of patients with DTC according to RRA timing. DESIGN RETROSPECTIVE STUDY PATIENTS: A total of 107 TNM stage 1 DTC patients were divided into two groups. In group A (n = 50), RRA was administered in less than 4·7 months median 3·0 (range 0·8-4·7), while in group B (n = 57) in more than 4·7 months median 6 (4·8-30·3) after thyroidectomy. Remission was achieved when stimulated serum Tg levels were undetectable, in the absence of local recurrence or cervical lymph node metastases on the neck ultrasound. RESULTS: All patients underwent near-total thyroidectomy. The mean age at diagnosis was 49·3 years (range: 18-79 years). There were no statistically significant differences in the histological subtype, the TNM stage, the dose of radioiodine and the time of follow-up, between the two groups. After the RRA treatment, 44 group A patients (88%) were in remission and 6 (12%) in persistence; while in group B, 52 (91·2%) were in remission, 1 (1·8%) in persistence and 4 (7%) in recurrence. At their latest follow-up median 87·3 (23·3-251·6 months), all patients were in remission, either as a result of further iodine radioiodine therapy (in 11 patients) or watchful monitoring. CONCLUSIONS: The timing of RRA seems to have no effect on the long-term outcome of the disease. Therefore, urgency for radioiodine ablation in patients with low-risk thyroid cancer is not recommended.

(18)F-FDG-PET/CT, (123)I-MIBG and (99m)Tc-MDP whole-body scans, in detecting recurrence of an adult adrenal neuroblastoma.

Neuroblastoma is the most common extracranial solid malignancy in children, but is rare in adults. We report the case of a 33 year old man with recurrence of neuroblastoma, 2 years after the excision of the primary tumor in the right adrenal gland. The iodine-123-radioiodinated metaiodobenzylguanidine ((123)I-MIBG) and (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) bone scans and the fluorine-18-fluorodeoxyglucose-positron computed tomography ((18)F-FDG PET/CT) findings in this patient are presented. First, we applied (123)I-MIBG scintigraphy that detected increased uptake at the right adrenal gland region and probably at liver lesions and in several bones. Then, the (99m)Tc-MDP bone scan revealed also increased uptake of the radiopharmaceutical in bones, but there was a discrepancy between these two studies concerning the number and location of the lesions. Then, (18)F-FDG PET/CT scan was performed, which showed increased uptake of (18)F-FDG at the right adrenal gland region with extension to the liver and also in multiple bones. Additionally, an aortocaval lymph node was detected. In conclusion, this case indicated that (18)F-FDG PET/CT has defined the extent of the recurrence of neuroblastoma in a better way than (123)I-MIBG and (99m)Tc-MDP together.

A robust method, based on a novel source, for performance and diagnostic capabilities assessment of the positron emission tomography system.

The aim of our work was to provide a robust method for evaluating imaging performance of positron emission tomography (PET) systems and particularly to estimate the modulation transfer function (MTF) using the line spread function (LSF) method. A novel plane source was prepared using thin layer chromatography (TLC) of a fluorine-18-fluorodeoxyglucose ((18)F-FDG) solution. The source was placed within a phantom, and imaged using the whole body (WB) two dimensional (2D) and three dimensional (3D) standard imaging protocols in a GE Discovery ST hybrid PET/CT scanner. Modulation transfer function was evaluated by determining the LSF, for various reconstruction methods and filters. The proposed MTF measurement method was validated against the conventional method, based on point spread function (PSF). Higher MTF values were obtained with 3D scanning protocol and 3D iterative reconstruction algorithm. All MTF obtained using 3D reconstruction algorithms showed better preservation of higher frequencies than the 2D algorithms. They also exhibited better contrast and resolution. MTF derived from LSF were more precise compared with those obtained from PSF since their reproducibility was better in all cases, providing a mean standard deviation of 0.0043, in contrary to the PSF method which gave 0.0405. In conclusion, the proposed method is novel and easy to implement for characterization of the signal transfer properties and image quality of PET/computed tomography (CT) systems. It provides an easy way to evaluate the frequency response of each kernel available. The proposed method requires cheap and easily accessible materials, available to the medical physicist in the nuclear medicine department. Furthermore, it is robust to aliasing and since this method is based on the LSF, is more resilient to noise due to greater data averaging than conventional PSF-integration techniques.

Towards improved diagnosis: radiomics and quantitative biomarkers in 18F-PSMA-1007 and 18F-fluorocholine PET/CT for prostate cancer recurrence.

OBJECTIVE: This study compared the radiomic features and quantitative biomarkers of 18F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. METHODS: A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUVmean, PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. RESULTS: Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUVmax value was significantly higher for 18F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUVmean, TL-PSMA/FCH, and PSMA/FCH-TV as per table 2 between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUVmean/SUVmax and PSA level was moderate, both for 18F-PSMA (r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH (r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18F-PSMA (r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH (r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUVmax values for both radiotracers compared with those who did not, the difference was statistically significant only for 18F-PSMA (P < 0.05). CONCLUSION: Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.

One-year outcomes of resveratrol supplement with aflibercept versus aflibercept monotherapy in wet age-related macular degeneration.

AIM: To determine the one-year outcomes of resveratrol oral supplement in patients suffering from wet age-related macular degeneration (AMD). METHODS: Fifty naïve and previously untreated patients suffering from wet AMD, were randomly assigned in two subgroups of 25 patients each. All the participants were treated with 3 monthly intravitreal injections of 2.0 mg aflibercept (IAIs) followed by injections "according to need", while in one group the patients also received daily two tablets of resveratrol oral supplement. Prior to treatment initiation, a complete ophthalmological examination, including best corrected visual acuity (BCVA) and contrast sensitivity evaluation, optical coherence tomography (OCT) scans, fundus autofluorescence (FAF), fluorescein angiography, indocyanine green angiography, and OCT angiography (OCTA), was performed to every participant, while all of them completed the Hospital Anxiety and Depression Scale (HADS) questionnaire, in order to assess their quality of life (QoL) status. The patients were assessed monthly for 1y with FAF, and OCT or OCTA; the main endpoints were the number IAIs, the changes in BCVA, in contrast sensitivity, and in patients' QoL status. RESULTS: No significant differences were present between the groups regarding the baseline demographic and clinical data. Over the 12-month period, a similar number of IAIs was applied in both groups (4.52±1.00 vs 4.28±0.90, P=0.38), while the rest of the clinical data also did not differ significantly after the completion of the study period. However, for HADS Depression (11.88±2.51 vs 8.28±1.54, P<0.001) and HADS Anxiety (11.92±2.52 vs 7.76±1.51, P<0.001) questionnaires values, the score was significantly better in patients who received resveratrol supplements. Moreover, a statistically significant difference was detected in the mean change from baseline values of contrast sensitivity (0.17±0.19 vs 0.35±0.24, P=0.005), HADS Depression (0.08±1.38 vs -3.88±1.48, P<0.001), and HADS Anxiety (0.36±1.98 vs -5.12±2.70, P<0.001) scores, in favour of the patients treated with resveratrol supplements. CONCLUSION: The resveratrol oral supplement is a complementary treatment in cases of wet AMD, highlighting its effectiveness in improving patients' QoL status.

Comparison of 18F-PSMA-1007 and 18F-Choline PET/CT in prostate cancer patients with biochemical recurrence: a phase 3, prospective, multicenter, randomized study.

OBJECTIVES: This prospective, multicenter, open-label, randomized, crossover trial study was to evaluate the diagnostic performance of 18F-PSMA-1007 (PSMA) vs. 18F-Choline PET/CT (FCH) in prostate cancer (PCa) patients (pts) with biochemical recurrence (BCR). METHODS: One hundred eighty-six pts, who have undergone primary definitive treatment for PCa with BCR, were recruited to this prospective study. All pts underwent one PSMA and one FCH PET/CT examination in randomized order within a time frame of 8 days and were followed up for at least 6 months (182 ±â€…10 days). RESULTS: Recurrence of PCa was observed in 176 out of 186 pts. The overall correct detection rate (DR) was 84% (95% CI 0.7967-0.8830) for PSMA and 69% (95% CI 0.6191-0.7489) for FCH, yielding a difference in proportion of 16% ( P  < 0.0001). PSMA had a sensitivity of 0.8464 and FCH 0.6857 with an odds ratio of 2.5259 ( P  < 0.0001), with statistically significant greater sensitivity of PSMA (ORs, 2.7877 and 2.1283 respectively) ( P  < 0.0001). PET/CT imaging led to a more accurate diagnosis in 166 (89.2%) pts, of which PSMA had contributed more than FCH in 91 (54.8%) of them. The DR for cutoff point PSA ≤ 1 ng/ml was higher for PSMA compared to FCH (61.8% vs. 39.5%). DR value of 51.6% for PSMA reached at PSA ≤ 0.3 ng/ml, while FCH reached that DR value with PSA ≤ 2.2 ng/ml. CONCLUSION: 18F-PSMA-1007 is more efficacious than 18F-Choline for the identification metastatic lesions both in patient and in regional level analysis in PCa patients with BCR.

Preparation and Evaluation of 64Cu-Radiolabled Dual-Ligand Multifunctional Gold Nanoparticles for Tumor Theragnosis.

Gold nanoparticles (AuNPs) are cutting-edge platforms for combined diagnostic and therapeutic approaches due to their exquisite physicochemical and optical properties. Using the AuNPs physically produced by femtosecond pulsed laser ablation of bulk Au in deionized water, with a capping agent-free surface, the conjugation of functional ligands onto the AuNPs can be tunable between 0% and 100% coverage. By taking advantage of this property, AuNPs functionalized by two different types of active targeting ligands with predetermined ratios were fabricated. The quantitatively controllable conjugation to construct a mixed monolayer of multiple biological molecules at a certain ratio onto the surface of AuNPs was achieved and a chelator-free 64Cu-labeling method was developed. We report here the manufacture, radiosynthesis and bioevaluation of three different types of dual-ligand AuNPs functionalized with two distinct ligands selected from glucose, arginine-glycine-aspartate (RGD) peptide, and methotrexate (MTX) for tumor theragnosis. The preclinical evaluation demonstrated that tumor uptakes and retention of two components AuNP conjugates were higher than that of single-component AuNP conjugates. Notably, the glucose/MT- modified dual-ligand AuNP conjugates showed significant improvement in tumor uptake and retention. The novel nanoconjugates prepared in this study make it possible to integrate several modalities with a single AuNP for multimodality imaging and therapy, combining the power of chemo-, thermal- and radiation therapies together.

Biodistribution of intravenous [99mTc]Tc-phytate in mouse models of chemically and foreign-body induced sterile inflammation.

When injected intravenously, [99mTc]Tc-phytate forms particles in the nanometer range. This size can favor its extravasation into tumor and inflammation through pores of the vasculature. The aim of this work is the evaluation of the use of [99mTc]Tc-phytate to assess sterile inflammation in mouse models. Biodistribution studies of [99mTc]Tc-phytate were performed in two groups of male Swiss Albino mice. Sterile inflammation was induced after intramuscular injection of turpentine in the first group (chemically induced sterile inflammation model) and after implantation of sterile metal bolts in the second group (foreign-body induced sterile inflammation model). [99mTc]Tc-phytate was intravenously injected after the development of inflammation in both groups and ex vivo biodistribution of the radiolabelled complex followed at different time-points. Biodistribution was expressed as percent injected dose per gram (%ID/g). Target-to-background ratios were also recorded. For the chemically induced sterile inflammation model, ex vivo biodistribution evaluation measurements revealed a pronounced uptake in the inflamed muscle when compared to uptake in the control/non-inflamed muscle. Moreover, as expected, there is a high uptake in the liver and spleen. For the foreign-body induced sterile inflammation model, a significantly higher uptake was observed in the inflamed muscle post [99mTc]Tc-phytate injection, both for the 24 hours post-bolt implantation and for the 7 days post-bolt implantation groups. The nanoparticle properties of [99mTc]Tc-phytate are potentially useful in the imaging of different types of sterile inflammation with translational potential clinical SPECT (single photon emission computed tomography) imaging applications in humans.

Safety and tolerability of regadenoson compared with dipyridamole in myocardial perfusion imaging in patients scheduled to undergo medium to high-risk noncardiac surgery: a randomized controlled study.

OBJECTIVE: Regadenoson is the first Food and Drug Administration-approved selective A2A adenosine receptor agonist used in myocardial perfusion imaging. Its main benefits are its simplified and brief protocol, along with the ability to be administered safely in patients with asthma or chronic obstructive pulmonary disease of moderate severity. This study aims to identify any potential benefits of regadenoson, regarding the frequency of adverse reactions and its tolerability, over dipyridamole. METHODS: This is a randomized controlled study of 200 patients scheduled for medium to high-risk noncardiac surgery, of whom 100 were stressed with regadenoson (study group) and the rest with dipyridamole (control group). RESULTS: A greater proportion of adverse reactions was recorded in the regadenoson group as compared to the dipyridamole group (53 vs. 36%; P = 0.023), though the duration of most adverse reactions was shorter in the regadenoson group. Dyspnea (P < 0.001) and gastrointestinal disturbances (P = 0.001) were significantly more frequent in the regadenoson group. The use of aminophylline in patients who developed any adverse events was similar in the two groups (P > 0.05). When multiple regression analyses were performed, differences in adverse reactions between the two groups were no longer significant (odds ratio = 1.96; 95% confidence interval, 0.88-3.25; P = 0.11). CONCLUSION: In our group of patients scheduled for myocardial perfusion imaging for preoperative assessment, the two agents, regadenoson and dipyridamole, have no significant differences in the frequency of mild adverse reactions and in aminophylline use, with regadenoson also having the advantage of faster symptom resolution. Nevertheless, dipyridamole can be considered as a well-tolerated and low-cost alternative.

A Real-World, Multicenter, 6-Month Prospective Study in Greece of the Effectiveness and Safety of Ranibizumab in Patients with Age-Related Macular Degeneration Who Have Inadequately Responded to Aflibercept: The "ELEVATE" Study.

Purpose: Real-world evidence on short-term outcomes of ranibizumab in wet age-related macular degeneration (wAMD) following inadequate response to aflibercept is scarce. This study aimed to evaluate the functional and anatomic effects of switching to ranibizumab in cases of wAMD previously treated with aflibercept with inadequate response. Patients and Methods: Prospective, observational study performed in eight ophthalmology hospital/private clinics in Greece, enrolling consented patients with active wAMD, ≥50 years-old, who had initiated ranibizumab ≥28 days and <2 months after their last aflibercept injection. Data were collected at enrollment, and at 1, 3 and 6 months post-treatment onset (post-baseline). Results: Between September-2015 and November-2017, 103 eligible patients (56.3% females; mean age: 74.8±8.6 years) were consecutively enrolled. The age at AMD diagnosis in the study eye was 71.3±8.8 years. Aflibercept (median of 5 injections received over 11.3 months) had been discontinued for anatomical (in 69.9%) and/or functional (38.8%) reasons. At baseline (median: 24.3 months after wAMD diagnosis), choroidal neovascularization was occult in 69.1% of evaluable study eyes; 60.2% of the study eyes had pigment epithelial detachment (PED); 42.7% cysts; 21.4% fibrosis; 66.0% subretinal, and 59.2% intraretinal fluid. At 6 months post-baseline: a median of 3 ranibizumab injections (range: 1-6) had been received; the best-corrected visual acuity (BCVA)≥0 letter gain rate was 81.8%; the BCVA ≥15 letter gain rate was 17.0%; BCVA gain was 3.2 letters [mean increase: 3.2±10.0 letters; median: 0.0; p = 0.002]; PED greatest basal diameter (GBD; median: 1470.5 µm) also decreased (median decrease: 114.0 µm; p = 0.019). Baseline central retinal thickness (CRT; median: 312.0 µm) remained unchanged. One patient permanently discontinued ranibizumab due to adverse event occurrence, assessed as not causally related to ranibizumab. There were no ranibizumab-related adverse reactions. Conclusion: Six-month treatment with ranibizumab in aflibercept inadequate responders led to visual acuity and PED GBD improvements, with no statistically significant CRT change.