Comparison of quantitative whole body PET parameters on [68Ga]Ga-PSMA-11 PET/CT using ordered Subset Expectation Maximization (OSEM) vs. bayesian penalized likelihood (BPL) reconstruction algorithms in men with metastatic castration-resistant prostate cancer.

BACKGROUND: PSMA PET/CT is a predictive and prognostic biomarker for determining response to [177Lu]Lu-PSMA-617 in patients with metastatic castration resistant prostate cancer (mCRPC). Thresholds defined to date may not be generalizable to newer image reconstruction algorithms. Bayesian penalized likelihood (BPL) reconstruction algorithm is a novel reconstruction algorithm that may improve contrast whilst preventing introduction of image noise. The aim of this study is to compare the quantitative parameters obtained using BPL and the Ordered Subset Expectation Maximization (OSEM) reconstruction algorithms. METHODS: Fifty consecutive patients with mCRPC who underwent [68Ga]Ga-PSMA-11 PET/CT using OSEM reconstruction to assess suitability for [177Lu]Lu-PSMA-617 therapy were selected. BPL algorithm was then used retrospectively to reconstruct the same PET raw data. Quantitative and volumetric measurements such as tumour standardised uptake value (SUV)max, SUVmean and Molecular Tumour Volume (MTV-PSMA) were calculated on both reconstruction methods. Results were compared (Bland-Altman, Pearson correlation coefficient) including subgroups with low and high-volume disease burdens (MTV-PSMA cut-off 40 mL). RESULTS: The SUVmax and SUVmean were higher, and MTV-PSMA was lower in the BPL reconstructed images compared to the OSEM group, with a mean difference of 8.4 (17.5%), 0.7 (8.2%) and - 21.5 mL (-3.4%), respectively. There was a strong correlation between the calculated SUVmax, SUVmean, and MTV-PSMA values in the OSEM and BPL reconstructed images (Pearson r values of 0.98, 0.99, and 1.0, respectively). No patients were reclassified from low to high volume disease or vice versa when switching from OSEM to BPL reconstruction. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT quantitative and volumetric parameters produced by BPL and OSEM reconstruction methods are strongly correlated. Differences are proportional and small for SUVmean, which is used as a predictive biomarker. Our study suggests that both reconstruction methods are acceptable without clinical impact on quantitative or volumetric findings. For longitudinal comparison, committing to the same reconstruction method would be preferred to ensure consistency.

Manganese- and Platinum-Driven Oxidative and Nitrosative Stress in Oxaliplatin-Associated CIPN with Special Reference to Ca4Mn(DPDP)5, MnDPDP and DPDP.

Platinum-containing chemotherapeutic drugs are efficacious in many forms of cancer but are dose-restricted by serious side effects, of which peripheral neuropathy induced by oxidative-nitrosative-stress-mediated chain reactions is most disturbing. Recently, hope has been raised regarding the catalytic antioxidants mangafodipir (MnDPDP) and calmangafodipir [Ca4Mn(DPDP)5; PledOx®], which by mimicking mitochondrial manganese superoxide dismutase (MnSOD) may be expected to overcome oxaliplatin-associated chemotherapy-induced peripheral neuropathy (CIPN). Unfortunately, two recent phase III studies (POLAR A and M trials) applying Ca4Mn(DPDP)5 in colorectal cancer (CRC) patients receiving multiple cycles of FOLFOX6 (5-FU + oxaliplatin) failed to demonstrate efficacy. Instead of an anticipated 50% reduction in the incidence of CIPN in patients co-treated with Ca4Mn(DPDP)5, a statistically significant increase of about 50% was seen. The current article deals with confusing differences between early and positive findings with MnDPDP in comparison to the recent findings with Ca4Mn(DPDP)5. The POLAR failure may also reveal important mechanisms behind oxaliplatin-associated CIPN itself. Thus, exacerbated neurotoxicity in patients receiving Ca4Mn(DPDP)5 may be explained by redox interactions between Pt2+ and Mn2+ and subtle oxidative-nitrosative chain reactions. In peripheral sensory nerves, Pt2+ presumably leads to oxidation of the Mn2+ from Ca4Mn(DPDP)5 as well as from Mn2+ in MnSOD and other endogenous sources. Thereafter, Mn3+ may be oxidized by peroxynitrite (ONOO-) into Mn4+, which drives site-specific nitration of tyrosine (Tyr) 34 in the MnSOD enzyme. Conformational changes of MnSOD then lead to the closure of the superoxide (O2•-) access channel. A similar metal-driven nitration of Tyr74 in cytochrome c will cause an irreversible disruption of electron transport. Altogether, these events may uncover important steps in the mechanism behind Pt2+-associated CIPN. There is little doubt that the efficacy of MnDPDP and its therapeutic improved counterpart Ca4Mn(DPDP)5 mainly depends on their MnSOD-mimetic activity when it comes to their potential use as rescue medicines during, e.g., acute myocardial infarction. However, pharmacokinetic considerations suggest that the efficacy of MnDPDP on Pt2+-associated neurotoxicity depends on another action of this drug. Electron paramagnetic resonance (EPR) studies have demonstrated that Pt2+ outcompetes Mn2+ and endogenous Zn2+ in binding to fodipir (DPDP), hence suggesting that the previously reported protective efficacy of MnDPDP against CIPN is a result of chelation and elimination of Pt2+ by DPDP, which in turn suggests that Mn2+ is unnecessary for efficacy when it comes to oxaliplatin-associated CIPN.

A pictorial view on false positive findings of 68Ga-PSMA-11 PET/CT and their prognostic value in patients with prostate carcinoma after radical prostatectomy and undetectable PSA values.

OBJECTIVE: Recently, gallium-68-prostate-specific membrane antigen-11 (68Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) has become a key imaging method in prostate carcinoma staging and biochemical progression, with varying sensitivities in different studies (from 40% to 80%). After four years of experience with 68Ga-PSMA-11 PET/CT, we found that it is possible to detect lesions with increased PSMA expression in patients with undetectable prostate specific antigen (PSA) levels after radical prostatectomy. The key questions we wanted to answer were as follows: if those lesions were malignant and could the early detection of those malignant lesions have a role in patient management? We aimed to identify and follow up PSMA-positive findings for a period of 4 years in patients with prostate cancer after radical prostatectomy and undetectable PSA values at the time of the examination. We also explored false-positive lesions in detail. SUBJECTS AND METHODS: The study included all patients who underwent radical prostatectomy and had undetectable PSA values <0.05ng/mL and who underwent 68Ga-PSMA-11 PET/CT between July 2019 and December 2019. We performed 220 studies and found 40 patients with these characteristics; these patients were included in this study. All of them were followed up until July 2023. Any finding with increased radiopharmaceutical accumulation above the background activity in the respective area was considered a false positive. Prostate-specific membrane antigen accumulation in established lesions was assessed semi-quantitatively by the maximum standardized uptake value (SUVmax) and qualitatively by the four-point visual scale proposed in the E-PSMA recommendations. RESULTS: We found 15/40 (37.5%) patients with PSMA-positive findings. These were predominantly bone changes without a corresponding CT abnormality or discrete cystic or osteoblastic lesions with above-background increased PSMA expression. The mean SUVmax of these non-specific lesions was 3.02 (SD 2.86). After 3.5-4 years of follow-up, biochemical progression was found in only two of the patients.The great sensitivity of the method nowadays is a powerful engine for the development of new therapeutic options. On the other side, the lower specificity due to false positive findings, if misinterpreted, might lead to switching to a higher stage, with the planned radical treatment replaced by palliative treatment. CONCLUSION: The presence of 68Ga-PSMA-11 PET/CT-positive findings in patients after radical prostatectomy and an undetectable PSA had a low predictive value for future progression. The interpretation of 68Ga-PSMA-11 PET/CT should always include a complex assessment of the clinical setting-the risk group, PSA value and degree of PSMA accumulation in the lesions. In these situations, further clarification of PSMA-positive findings is appropriate before deciding to change treatment.

Clinical utility of [68Ga]Ga-PSMA-11 PET/CT in initial staging of patients with prostate cancer and importance of intraprostatic SUVmax values.

BACKGROUND: As in disease recurrence, providing clinicians with the exact extent of the disease at the time of initial diagnosis is key in the management and individual treatment of prostate cancer (PC) patients. Intending to examine the usefulness of gallium- 68 PSMA-11 positron emission tomography/computed tomography ([68Ga]Ga-PSMA-11 PET/CT) and to determine if there is a correlation between prostate-specific antigen (PSA) serum values, WHO/ISUP (World Health Organization/International Society of Urological Pathology's) grade group of the tumor and SUVmax (maximized standardized uptake value) values we retrospectively analyzed PET/CT studies performed for initial staging of the disease. PATIENTS AND METHODS: We retrospectively evaluated 34 studies of patients who underwent [68Ga]Ga-PSMA-11 PET/CT as part of the initial staging of prostate cancer. All patients had prostate cancer confirmed by histological assessment after biopsy and had Gleason score and PSA serum values obtained. The mean PSA value was 33.8 ± 40.9 nmol/L (range 2.2-232). RESULTS: Nineteen patients had extended disease (55.9%). The mean SUVmax in prostate lesions was 19.5 ± 12.6. The mean value of SUVmax of PET studies in the high-risk group was significantly higher than those of low risk (23.5 ± 13.2 and 10.6 ± 5.4, p < 0.05). A positive correlation was observed between the ISUP group and SUVmax value of prostate lesions (Pearson's r = 0.557, p < 0.01). A positive correlation was also found in the comparison between PSA values and SUVmax (Pearson's r = 0.34, p < 0.05). CONCLUSIONS: In our study, [68Ga]Ga-PSMA-11 PET/CT scans detected the extended disease in more than half of the patients. Locating disease beyond the prostate gland allowed better informed clinical decisions and modified treatment. A positive correlation was found between intraprostatic SUVmax values and the ISUP group of prostate cancer. High-risk patients had SUVmax values that were significantly higher than those of low-risk patients. The correlation between the Gleason score and SUVmax value can be explained by the increased intensity of PSMA expression as the tumor grade increases.

Cutaneous, Subcutaneous, and Bilateral Adrenal Gland Metastases in Progressive Prostate Carcinoma: Theranostic Potential of 68 Ga-PSMA-11 PET/CT Imaging and 177 Lu-PSMA-617 Therapy.

ABSTRACT: Prostate carcinoma (PC) is the second most common malignant tumor in males globally. The metastatic spread of PC usually involves the pelvic and abdominal lymph nodes and the skeletal system. Cutaneous metastases are exceedingly uncommon and typically manifest themselves late in the disease course, considered as ominous sign with limited treatment options and a poor prognosis. We describe a patient wherein 68 Ga-PSMA-11 PET/CT detected multiple uncommon metastatic sites in the cutaneous region of the scrotum, penis, and thigh, as well as in the subcutaneous region of anterior abdominal wall, and in bilateral adrenal glands. These findings served as a theranostic tool for selecting 177 Lu-PSMA-617 treatment for these extremely rare metastatic sites.

Theranostic Agent Targeting Bone Metastasis: A Novel [68Ga]Ga/[177Lu]Lu-DOTA-HBED-bisphosphonate.

Bone metastasis in cancer patients is a major disease advancement for various types of cancer. Previously, [68Ga]Ga-HBED-CC-bisphosphonate ([68Ga]Ga-P15-041) showed excellent bone uptake and efficient detection of bone metastasis in patients. To accommodate different α- or ß--emitting metals for radionuclide therapy, a novel DOTA-HBED-CC-bisphosphonate (P15-073, 1) was prepared and the corresponding [68Ga]Ga-1 and [177Lu]Lu-1 were successfully synthesized in high yields and purity. Gallium-68 conjugation to HBED-CC at room temperature and lutetium-177 conjugation to DOTA at 95 °C were verified in model compounds through secondary mass confirmation. These bisphosphonates, [68Ga]Ga-1 and [177Lu]Lu-1, displayed high binding affinity to hydroxyapatite in vitro. After an iv injection, it showed excellent uptake in the spine of normal mice, and micro-PET/CT imaging of nude mice model of bone metastasis showed high bone uptake in tumor tissue. The results indicated that [68Ga]Ga/[177Lu]Lu-1 holds promise as a theranostic radioligand agent for managing cancer bone metastases.

Business continuity plan in the management and operations of hospitals: First experience to certify the PDTA processes with the requirements defined by ISO 22301:2019 in emergency medical services.

BACKGROUND: A business continuity plan (BCP) facilitates the performance of primary functions during emergencies or other situations that can disrupt normal operations. If risk management is done analytically, a business impact analysis (BIA), according to ISO 22301 certification, makes it possible to define the best strategy for supporting the company's assets and image, optimizing the operational efficiency of service recovery and redesigning spaces for health. Since 2015, our healthcare company has embarked on a certification process for all sectors and activities through the implementation and development of diagnostic and therapeutic paths for operational diagnos-tic-therapeutic-assistance pathways (PDTAs). PDTA processes are all certified by the ISO 9001:2015 management system hospital. Our hospital is the first healthcare company to have obtained ISO 22301:2019 certification concerning PDTA processes, offering patients the highest standards of quality and safety of care in emergency medical services. METHODS: The formal BCP process includes several steps prior to the creation of a BCP: create a BCP team, conduct a BIA, determine the continuity plan by using the results of the analyses, and conduct training and exercises to educate staff and improve the BCP. RESULTS: From the BIA analysis, the team identified the time-employee PDTAs in company paths under emergency and urgency: acute ST-elevation myocardial infarction (STEMI), TRAUMA, and STROKE, providing for a planning path that took advantage of the duration of approximately 12 months. This path included the creation of structural procedures, the redefinition and updating of the PDTA in the light of the BCP, the preparation of exercises aimed at guaranteeing the business continuity objectives, and, finally, the awareness of our stakeholders regarding its correct application. CONCLUSIONS: With a business continuity management (BCM) system, companies take preventative measures to ensure they can start operations again quickly in an emergency. An exhaustive BIA in a hospital company reveals the effects when processes fail, how critical each process is for the company, and the amount of time required to get up and running again, thus providing the organization with important information for risk management. The measures for handling risks derived from this analysis are incorporated into a BCM system where the emergency plans are defined, too, so that business operations continue even in the event of an emergency.

Pregnancy and obstetric outcomes of dichorionic triamniotic triplet pregnancies with selective foetal reduction after assisted reproductive technology.

BACKGROUND: It is generally beneficial and recommended that dichorionic triamniotic (DCTA) triplet pregnancies be reduced to monochorionic (MC) twin or singleton pregnancies after assisted reproductive technology (ART). However, some infertile couples still have a firm desire to retain twins. For this reason, the best foetal reduction strategies need to be available for infertile couples and clinicians. Given that data on the elective reduction of DCTA triplet pregnancies to twin pregnancies are scarce, we investigated the outcomes of elective reduction of DCTA triplet pregnancies through the retrospective analysis of previous data. METHOD: Patients with DCTA triplet pregnancies who underwent elective foetal reduction between January 2012 and June 2020 were recruited. A total of 67 eligible patients with DCTA triplet pregnancies were divided into two groups: a DCTA-to-dichorionic diamniotic (DCDA) twin group (n = 38) and a DCTA-to-monochorionic diamniotic (MCDA) twin group (n = 29); the basic clinical data of the two groups were collected for comparison. RESULTS: Compared with the DCDA-to-MCDA twin group, the DCTA-to-DCDA twin group had lower rates of complete miscarriage (7.89% versus 31.03%, p = 0.014), early complete miscarriage (5.26% versus 24.14%, p = 0.034), late preterm birth (25.71% versus 65.00%, p = 0.009) and very low birth weight (0 versus 11.11%, p = 0.025). In addition, the DCTA-to-DCDA twin group had higher rates of full-term delivery (65.71% versus 25.00%, p = 0.005), survival (92.11% versus 68.97%, p = 0.023), and taking the babies home (92.11% versus 68.97%, p = 0.023) than did the DCTA-to-MCDA twin group. In terms of neonatal outcomes, a significantly greater gestational age (38.06 ± 2.39 versus 36.28 ± 2.30, p = 0.009), average birth weight (3020.77 ± 497.33 versus 2401.39 ± 570.48, p < 0.001), weight of twins (2746.47 ± 339.64 versus 2251.56 ± 391.26, p < 0.001), weight of the larger neonate (2832.94 ± 320.58 versus 2376.25 ± 349.95, p < 0.001) and weight of the smaller neonate (2660.00 ± 345.34 versus 2126.88 ± 400.93, p < 0.001) was observed in the DCTA-to-DCDA twin group compared to the DCTA-to-MCDA twin group. CONCLUSION: The DCTA-to-DCDA twin group had better pregnancy and neonatal outcomes than the DCTA-to-MCDA twin group. This reduction approach may be beneficial for patients with dichorionic triamniotic triplet pregnancies who have a strong desire to have DCDA twins.

An Unexpected Seminal Vesicle Pitfall in PSMA PET.

ABSTRACT: A 76-year-old man undergoing hormone therapy for prostate cancer was referred for 68 Ga-PSMA-11-PET (PSMA PET) due to persistently detectable PSA level. No PSMA-positive tumor lesions were detected, so a delayed phase imaging was performed, which revealed focal PSMA uptake in the right seminal vesicle together with contrast accumulation on excretory phase contrast-enhanced CT. These findings were finally determined to be secondary to urinary reflux as a consequence of a prostatic enucleation he had undergone 5 months earlier following an episode of acute urinary retention.

A Hangover Under 177 Lu-PSMA-617 Therapy : A Red Flag for Brain 68 Ga-PSMA-11 PET/MRI?

ABSTRACT: Leptomeningeal carcinomatosis in prostate cancer is extremely rare. Because of the low overall penetration of drugs into the brain and the prolonged survival of castration-resistant prostate cancer (CRPC) patients, a special attention should be paid to the appearance of neurological symptoms in long-term CRPC survivors. A patient suffering from a CRPC with bone metastases underwent 4 cycles of 177 Lu-PSMA (prostate-specific membrane antigen)-617. Starting from the third cycle, he reported an increasing feeling of a permanent hangover. A 68 Ga-PSMA-11 brain PET/MRI was carried out after the fourth cycle. It revealed intraparenchymatous brain metastases with intense uptake and evidences of leptomeningeal carcinomatosis.

68 Ga-PSMA Uptake in the Testis : Two Different Patients With Two Different Diagnosis.

ABSTRACT: Although abnormal 68 Ga-PSMA uptake in the prostate and its metastases can be seen in a variety of diseases, it is rare to see in the testis. In these 2 cases, 68 Ga-PSMA PET/CT revealed unilateral 68 Ga-PSMA uptake in the testis of 2 patients. One of these patients was diagnosed with testis metastases from prostate cancer after an orchiectomy. The other patient was diagnosed with an orchitis. 68 Ga-PSMA uptake should be considered as an infection, as well as a malignancy in the initial differential diagnosis.

A glycol chitosan derivative with extrafibrillar demineralization potential for self-etch dentin bonding.

OBJECTIVES: Extrafibrillar demineralization is an etching technique that removes only minerals from around the collagen fibrils for resin infiltration. The intrafibrillar minerals are left intact to avoid their replacement by water that is hard for adhesive resin monomers to displace. The present work reported the synthesis of a water-soluble methacryloyloxy glycol chitosan-EDTA conjugate (GCE-MA) and evaluated its potential as an extrafibrillar demineralization agent for self-etch dentin bonding. METHODS: Glycol chitosan-EDTA was functionalized with a methacryloyloxy functionality. Conjugation was confirmed using Fourier transform-infrared spectroscopy. The GCE-MA was used to prepare experimental self-etch primers. Extrafibrillar demineralization of the primers was evaluated with scaning electron microscopy and transmission electron microscopy. The feasibility of this new self-etch bonding approach was evaluated using microtensile bond strength testing and inhibition of dentin gelatinolytic activity. The antibacterial activity and cytotoxicity of GCE-MA were also analyzed. RESULTS: Conjugation of EDTA and the methacryloyloxy functionality to glycol chitosan was successful. The functionalized conjugate was capable of extrafibrillar demineralization of mineralized collagen fibrils. Tensile bond strength of the experimental self-etch primer to dentin was comparable to that of phosphoric acid-etched dentin and the commercial self-etch primer Clearfil SE Bond 2. The GCE-MA also inhibited soluble rhMMP-9. In-situ zymography detected minimal fluorescence in hybrid layers conditioned with the experimental primer. The GCE-MA was noncytotoxic and possessed antibacterial activities against planktonic bacteria. SIGNIFICANCE: Synthesis of GCE-MA brought into fruition a self-etch conditioner that selectively demineralizes the extrafibrillar mineral component of dentin. A self-etch primer prepared with GCE-MA achieved bond strengths comparable to commercial reference adhesive systems.

The Theranostic Optimization of PSMA-GCK01 Does Not Compromise the Imaging Characteristics of [99mTc]Tc-PSMA-GCK01 Compared to Dedicated Diagnostic [99mTc]Tc-EDDA/HYNIC-iPSMA in Prostate Cancer.

PURPOSE: Radiolabeled PSMA-ligands play a major role in today's nuclear medicine. Since approval of [177Lu]Lu-PSMA-617 for therapy of metastatic prostate cancer, availability of 177Lu became bottleneck of supply due to the high demand. Recently, a theranostic PSMA-ligand, PSMA-GCK01, was developed which can be labeled either diagnostically with 99mTc or therapeutically with 188Re with both nuclides available from well-known generator systems. This novel tracer might aid to overcome aforementioned supply limitations. In this investigation, the biodistribution and general imaging characteristics of [99mTc]Tc-PSMA-GCK01 were compared with the diagnostic reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA in patients with advanced stage prostate cancer. In addition, the binding of both ligands to PSMA was analyzed at the molecular level using molecular docking. PROCEDURES: Two cohorts (n = 19 vs. n = 21) of patients with metastatic castration-resistant prostate cancer matched for age, tumor stage, and Gleason score underwent a planar gamma camera imaging with [99mTc]Tc-EDDA/HYNIC-iPSMA or [99mTc]Tc-PSMA-GCK01 prior to PSMA-ligand therapy for PSMA-phenotyping. The imaging data were retrospective analyzed for salivary gland, kidney, liver, soft tissue, and tumor uptake on a semi-automated ROI-analysis using HERMES Medical Solutions AB (HMS, Sweden). RESULTS: The data sets were semi-automated quantified on a ROI-based analysis. The tumor-to-background presented equal results of [99mTc]Tc-PSMA-GCK01 compared to [99mTc]Tc-EDDA/HYNIC-iPSMA. The physiological PSMA-positive organs like salivary gland presented also equal uptake in counts/MBq (salivary gland median 9.48 [99mTc]Tc-PSMA-GCK01 vs. median 9.11 [99mTc]Tc-EDDA/HYNIC-iPSMA), while liver-to-kidney ratio presented a slight shift to the liver parenchyma using [99mTc]Tc-PSMA-GCK01 (0.83) compared to [99mTc]Tc-EDDA/HYNIC-iPSMA (0.55) with no statistical significance. This is in agreement with the results from the docking study revealing only a minor difference in the docking scores for both ligands. CONCLUSIONS: The novel theranostic tracer [99mTc]Tc/[188Re]Re-PSMA-GCK01 demonstrates comparable general imaging characteristic with the reference compound [99mTc]Tc-EDDA/HYNIC-iPSMA. These results pave the way for the PSMA-targeting imaging and theranostic agents for a broader, rather low-cost, generator applied radio-ligand therapy utilization.

Elongation of the proximal descending thoracic aorta and associated hemodynamics increase the risk of acute type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (ATBAD) is a life-threatening aortic disease. However, little information is available on predicting and understanding of ATBAD. OBJECTIVE: The study sought to explore the underlying mechanism of ATBAD by analyzing the morphological and hemodynamic characteristics related to aortic length. METHODS: The length and tortuosity of the segment and the whole aorta in the ATBAD group (n= 163) and control group (n= 120) were measured. A fixed anatomic landmark from the distal of left subclavian artery (LSA) to the superior border of sixth thoracic vertebra was proposed as the proximal descending thoracic aorta (PDTA), and the dimensionless parameter, length ratio, was introduced to eliminate the individual differences. The significant morphological parameters were filtrated and the associations between parameters were investigated using statistical approaches. Furthermore, how aortic morphology influenced ATBAD was explored based on idealized aortic models and hemodynamic-related metrics. RESULTS: The PDTA length was significantly increased in the ATBAD group compared with the control group and had a strong positive correlation with the whole aortic length (r= 0.89). The length ratio (LR2) and tortuosity (T2) of PDTA in the ATBAD group were significantly increased (0.15 ± 0.02 vs 0.12 ± 0.02 and 1.73 ± 0.48 vs 1.50 ± 0.36; P< 0.001), and LR2 was positive correlation with T2 (r= 0.73). In receiver-operating curve analysis, the area under the curve was 0.835 for LR2 and 0.641 for T2. Low and oscillatory shear (LOS) was positive correlation with LR2, and the elevated LOS occurred in the distal of LSA. CONCLUSION: Elongation of PDTA is associated with ATBAD, and the length ratio is a novel predictor. Elongated PDTA induced more aggressive hemodynamic forces, and high LOS regions may correspond to the entry tear location. The synergy of the morphological variation and aggressive hemodynamics creates contributory conditions for ATBAD.

PPY-cell hyperplasia accompanying NENs: Immunohistochemical and nuclear medicine analysis.

Pancreatic polypeptide cell hyperplasia (PPY-H) is a multiplication of the neuroendocrine cells producing pancreatic polypeptide (PPY). The development and role of PPY-H and its corresponding clinical and imaging findings still need to be fully elucidated. We present 12 cases of PPY-H accompanying pancreatic neuroendocrine neoplasias (NEN). PPY-H was analyzed with the help of immunohistochemistry and confocal microscopy; preoperative clinical data and imaging studies were evaluated retrospectively. We observed PPY-H emerging from pancreatic ducts, and in some cases, we observed simultaneous NKX6.1 positivity in ducts and PPY-H. Additional clinical-pathological correlations suggests that gastrointestinal symptoms (e.g., epigastric pain and cholestasis) could be more related to PPY-H than to NEN hormonal production. In particular cases, SSTR2 expression was strong in PPY-H and correlated with distinguishable accumulation of activity next to NEN on 99 mTc EDDA/Hynic-TOC SPECT/CT. In another case, 18F-FDG-PET/CT showed increased metabolic activity in the area of PPY-H surrounding NEN. Our data suggest that PPY-H originates in the lining of pancreatic ducts. Confirmation of SSTR2 in PPY-H, using immunohistochemistry, suggests the utility of 99 mTc EDDA/Hynic-TOC or 68Ga-DOTA radiotracers in clinical diagnostics; however, studies with larger cohort are needed.

Prevalence and distribution of pathogenic genes in Campylobacter jejuni isolated from poultry and human sources.

INTRODUCTION: Campylobacter jejuni is one of the most common bacterial causes of human gastroenteritis. Despite its public health importance, the virulence factors and mechanisms underlying C. jejuni pathogenesis remain poorly understood and the relationships between these genes and the sources of the strains are not clear. We aimed to determine the virulence profiles of C. jejuni isolated from poultry and human cases of Campylobacteriosis. METHODOLOGY: A total of 50 strains of C. jejuni isolated from poultry and human cases of Campylobacteriosis were screened by polymerase chain reaction (PCR) for the presence of six pathogenic genes (flaA, iam, wlaN, cdtA, cdtB, cdtC). RESULTS: A total of 40% (10/25) of the human isolates presented only one virulence marker. In contrast, 64% (16/25) of the poultry-derived strains showed four or five virulence markers. cdtA and flaA occurred more frequently in poultry-derived strains than in human strains. Ten different virulence profiles were observed among the human isolates and 11 among the poultry strains. Only four profiles were common to both sources: profiles 3 (flaA, cdtA, cdtB, and cdtC), 5 (cdtA and cdtB), 7 (flaA and cdtB), and 10 (iam, flaA, cdtA, cdtB, and cdtC). The human-derived strains had a higher Shannon diversity index (1.9396) and Simpson index (0.8367), indicating a more diversified population than found in poultry (1.7742 and 0.7333, respectively). CONCLUSIONS: We found variations in the genetic profiles of the circulating strains based on the isolation source and genes that are potentially pathogenic to humans were detected in poultry-derived strains.

New PSMA-Targeting Ligands: Transformation from Diagnosis (Ga-68) to Radionuclide Therapy (Lu-177).

Prostate-specific membrane antigen (PSMA) is a promising target for the diagnosis and radionuclide therapy of prostate cancer. This study reports conversion of a previously reported 68Ga-imaging agent, [68Ga]Ga-P16-093, to a Lu-177 radionuclide therapeutic agent. Substitution of the HBED-CC metal chelating group with DOTA(GA)2 led to P17-087 (4) and P17-088 (7). Both agents showed excellent PSMA binding affinity (IC50 = 10-30 nM) comparable to that of recently FDA-approved [177Lu]Lu-PSMA-617 (Pluvicto). Biodistribution studies in PSMA expressing tumor bearing mice showed that [177Lu]Lu-4 exhibited very high tumor uptake and a fast blood clearance similar to those of [177Lu]Lu-PSMA-617. Conversely, [177Lu]Lu-7, containing an albumin binder, extended its blood half-life and exhibited significantly higher uptake and longer tumor residence time than [177Lu]Lu-4 and [177Lu]Lu-PSMA-617. The switch from chelator HBED-CC to DOTA(GA)2 and the switch from the imaging isotope gallium-68 to the therapeutic isotope lutetium-177 have successfully transformed a PSMA-targeting agent from diagnosis to promising radionuclide therapeutic agents.

Ligand Steric Interactions Modulate Multidentate Ligand Exchange Pathways: Kinetics of Nickel(II) Ion Capture from N-Substituted IDA Complexes by CDTA.

Exchange reactions between multidentate ligands (also known as chelating agents) contribute to kinetic control of metal ion speciation in aquatic environments. However, the complexity of the stepwise reaction mechanism complicates predictions of kinetic behavior (rates, rate laws, and mechanisms). Clarity is achieved with the adjunctive-semijunctive-disjunctive paradigm, which categorizes multidentate ligand exchange pathways along a continuum according to the decreasing ease of forming intermediate mixed-ligand ternary complexes. In order to better understand how steric interaction between entering and leaving ligands affects reaction pathways and kinetic behavior, we use a capillary electrophoresis method to monitor exchange between trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetate (CDTA) and nickel(II) complexes with each of the following N-substituted iminodiacetate ligands (XIDA), iminodiacetate (IDA), methyliminodiacetate (MIDA), and benzyliminodiacetate (BIDA). Kinetic modeling indicates that reactions between CDTA and 1:1 nickel-XIDA complexes occur via parallel adjunctive and disjunctive pathways. With greater steric bulk of N-substituents on iminodiacetate, product formation via a disjunctive pathway increases while formation via the adjunctive pathway decreases. Kinetic analysis demonstrates how the shift in reaction pathways has a nonlinear effect on both the magnitude of the overall rate and the rate dependence on ligand concentrations. Furthermore, we discuss the implications of this work for understanding dynamic metal ion speciation in the environment.

Comparison of Internal Dosimetry of 18 F-PSMA-1007 and 68 Ga-PSMA-11-HBED-CC.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men worldwide. Targeting prostate-specific membrane antigen (PSMA) using radiopharmaceuticals has shown promising results for PCa imaging as well as theranostics. 68 Ga-based PSMA imaging is limited by production of small quantities by generator, and it has led to quest for cyclotron produced 18 F-based PSMA ligands. In the current study, we evaluated the biodistribution and internal dosimetry of 18 F-PSMA-1007 and compared it with 68 Ga-PSMA-11-HBED-CC. MATERIALS AND METHODS: A total of 8 patients with histopathologically proven PCa were included in the study, of whom 4 patients underwent 18 F-PSMA-1007, and the other 4 patients underwent 68 Ga-PSMA-11-HBED-CC PET/CT. The biodistribution of both tracers was quantified for different organs by computing SUVs. All the patients underwent 5-point serial imaging to compute equivalent dose to essential organs and whole-body effective dose using OLINDA-based dosimetry. RESULTS: The radiotracer uptake in brain, lacrimal gland, salivary gland, heart, lung, liver, gallbladder, spleen, pancreas, intestine, gluteal muscle, and bone marrow were found to be higher in 18 F-PSMA-1007 PET as compared with 68 Ga PSMA-11 PET. Kidney and urinary bladder showed higher SUV value on 68 Ga-PSMA-11-HBED-CC as compared with 18 F-PSMA-1007.The whole-body effective dose from 18 F-PSMA-1007 (1.46E-02 mSv/MBq) was higher than 68 Ga-PSMA-11-HBED-CC (1.03E-02 mSv/MBq). The highest mean equivalent dose from 18 F-PSMA-1007 was observed in the kidneys (1.48E-01 mGy/MBq), followed by spleen (mean, 1.06E-01 mGy/MBq) and liver (6.80E-02 mGy/MBq), whereas 68 Ga-PSMA-11-HBED-CC equivalent dose was maximum in the kidneys (2.13E-01 mGy/MBq), followed by liver (3.03E-02 mGy/MBq), spleen (2.90E-02 mGy/MBq), adrenals (2.67E-02 mGy/MBq), and urinary bladder (1.89E-02 mGy/MBq). CONCLUSION: Whole-body effective dose from 18 F-PSMA-1007 is higher compared with 68 Ga-PSMA-11-HBED-CC. 18 F-PSMA-1007 shows lesser urinary bladder clearance compared with 68 Ga-PSMA-11-HBED-CC, which can allow better interpretation of prostatic bed without significant radioactive urine interference. 18 F-PSMA-1007 is a cyclotron-produced alternative to generator-produced 68 Ga-PSMA-11-HBED-CC and can emerge as a good diagnostic surrogate for patients planned for 177 Lu-PSMA-617 therapy.

Safety and efficacy of a novel iron chelator (HBED; (N,N'-Di(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid)) in equine (Equus caballus) as a model for black rhinoceros (Diceros bicornis).

While iron overload disorder (IOD) and related disease states are not considered a common occurrence in domestic equids, these issues appear prevalent in black rhinoceroses under human care. In addressing IOD in black rhinos, altering dietary iron absorption and excretion may be the most globally practical approach. A main option for treatment used across other species such as humans, is chelation therapy using iron-specific synthetic compounds. As horses may serve as an appropriate digestive model for the endangered rhinoceros, we evaluated the potential use of the oral iron chelator N,N-bis(2-hydroxybenzyl)ethylenediamine-N,N-diacetic acid (HBED) in horses for safety and efficacy prior to testing in black rhinoceros. Health and iron digestibility and dynamics were assessed in horses (n = 6) before, and after treatment with HBED (50 mg/kg body weight) for 8 days using a crossover design with serum, faecal and urine collection. A preliminary pharmacokinetic trial was also performed but no trace of HBED was found in serially sampled plasma through 8 h post-oral dosing. HBED increased urinary iron output in horses compared to control by 0.7% of total iron intake (p < 0.01), for an average of 27 mg urinary iron/day, similar to human chelation goals. Blood chemistry, blood cell counts and overall wellness were not affected by treatment. As healthy horses are able to regulate iron absorption, the lack of change in iron balance is unsurprising. Short-term HBED administration appeared to be safely tolerated by horses, therefore it was anticipated it would also be safe to administer to black rhinos for the management of iron overload.