99mTc-PYP and 68Ga-FAPI PET/CT Images of Hereditary Transthyretin Amyloidosis With Cardiac Involvement.

ABSTRACT: Amyloidosis is a protein misfolding disorder characterized by the extracellular deposition of insoluble amyloid fibrils, derived from abnormally folded proteins. These fibrils disrupt tissue structure and function, leading to organ dysfunction. The condition encompasses various subtypes, each associated with distinct precursor proteins and clinical manifestations. 99mTc-PYP scintigraphy is used widely and holds significant importance for diagnosis. 68Ga-FAPI is also a promising radiotracer for various diseases. To our knowledge, this is the first case of a patient with hereditary transthyretin amyloidosis with cardiac involvement, which FAPI PET showed diffuse increased myocardial uptake.

US-guided percutaneous ablation of thyroid nodules with 177LU-MAA (LUTMA) - Feasibility study.

PURPOSE: The main purpose is to evaluate the safety, and efficacy of 177Lutetium labeled macroaggregated albumin (LUTMA) ablation of thyroid nodules. MATERIALS AND METHODS: Patients with confirmed benign nodules who were not candidate or did not accept surgery were enrolled. Under ultrasonography (USG) guidance, LUTMA which was produced in our department, was administered into the nodules. Nodule volumes were assessed via USG before the injection and at 1-week, 1-month, and 3-months post-treatment. We calculated the volume reduction rates (VRRs) for these intervals. To detect extranodular activity leakage, patients underwent SPECT/CT imaging at one hour, 24 h, and one week post-injection. RESULTS: Fifteen patients (male: 12, female: 3) with benign thyroid nodules were eligible to join this study. These nodules were categorized as cystic (n = 9), solid (n = 3), or mixed (n = 3). Median nodules volume was 6.59 ml (range: 0.56-55 ml). Predicted absorbed dosee to the nodules varied between 10-1036 Gy. The VRRs at 3 months was 85% for all nodule types with gradual increases over time: 0%-92%, 20%-97%, and 28%-98% at 1 week, 1 month, and 3-months, respectively. The median VRR of cystic nodules was 89% (range: 81%-98%) at 3-months. It is significantly higher than solid ones (P = .009). None of the patients experienced adverse reactions or discomfort during the injection or follow-up. CONCLUSION: LUTMA treatment significantly reduces the volume of benign thyroid nodules, offering relief from disease-associated symptoms and cosmetic concerns. It emerges as a promising alternative to surgical and other local treatments for benign thyroid nodule ablation. CLINICAL SIGNIFICATION: LUTMA is a novel theranostic radiopharmaceutical which is promising in local ablative treatment of benign thyroid nodules.

89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations.

BACKGROUND: The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium-89 (89Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood. RESULTS: The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30-60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered 89Zr-labelled leukocytes produced high-contrast murine PET images at 1 h-5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously 89Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [89Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo. CONCLUSIONS: Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies.

Hybrid Ga-68 prostate-specific membrane antigen PET/MRI in the detection of skeletal metastasis in patients with newly diagnosed prostate cancer: Contribution of each part to the diagnostic performance.

PURPOSE: Bone metastasis is essential in patients with prostate cancer (PCa) as it determines prognosis and survival. Hybrid PET/MRI allows simultaneous acquisition of PET and MRI data, thus combining the strength of both technologies allows the detection of bone marrow metastases that are missed by PET/CT. In this retrospective study, we aimed to evaluate the diagnostic efficiency of hybrid PET/MRI with Ga-68 prostate-specific membrane antigen (PSMA) in detecting skeletal metastases in newly diagnosed PCa patients and compared the effectiveness of stand-alone PSMA PET reviewing versus stand-alone whole-body (WB) MRI evaluation. We also investigated the effect of the interpretation of all PET/MR data together on clinical management. METHODS: We studied 74 newly diagnosed PCa patients who underwent PSMA PET/MRI for staging purposes. At first, PET and MRI were evaluated separately for bone lesions on a patient-and-lesion basis and then a further joint PSMA PET/MRI interpretation was made. RESULTS: Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy analysis for bone metastasis was, respectively, 1.0, 0.83, 0.54, 1.0, 0.86 for PET; 0.75, 0.96, 0.81, 0.95, 0.93 for WB MRI and 0.91, 0.95, 0.78, 0,98, 0.94 for PET/MRI. The combined PET/MRI evaluation changed the clinical impact in 13.5% of patients (eight correct and two wrong decisions) compared to PET stand-alone interpretation. CONCLUSION: PSMA PET imaging showed superior sensitivity to WB MRI in detecting bone metastases in newly diagnosed PCa patients, whereas WB MRI has superior specificity and PPV. Furthermore, the specificity and PPV of joint PET/MRI evaluation are better than PSMA PET alone. Despite the longer acquisition period, adding WB MRI sequences to PSMA PET imaging appears beneficial for PCa patient management.

Is there a potential biomarker in distinguishing invasive breast carcinomas with elevated Ki-67 levels among 2D-SWE, SMI, and 18F-FDG PET-CT/MRI-derived parameters?: A single-center data.

PURPOSE: To investigate the strength of quantitative imaging and metabolic parameters in differentiating invasive breast carcinomas with elevated Ki-67 levels. MATERIALS AND METHODS: A total of 123 patients with 129 breast lesions confirmed as invasive breast carcinoma underwent shear wave elastography (SWE), superb microvascular imaging (SMI) and positron emission tomography (PET)/CT or MRI. Adler's grade (classifying the microvascularity into four types) and Vascular Index (VI) was obtained by SMI as microvascular parameters. In addition, the stiffness value (Emean ) was evaluated in kilopascal by SWE. The average of consecutive measurements was recorded as mean VI and mean Emean . PET scan parameters were obtained as SUVmax and SULpeak . Lesions were divided into two groups according to the Ki-67 expression, low as ≤ 14 and high as >14. RESULTS: Adler's grading was the most correlated imaging parameter with high Ki-67 expression (p < 0.05), while VI and Emean had poor correlation (p > 0.05). SUVmax and SULpeak indicated a significant linear correlation with Ki-67 but a moderate correlation with the high levels of Ki-67 (p < 0,001). The sensitivity of VI, Emean , SUVmax and SULpeak was 64.6%, 66.7%, 65.7%, and 66.7% when the cut-off point was set to 5.25, 102.5, 6.59, and 2.63, respectively. SUVmax had the highest AUC value of 0.740, according to the ROC curve analysis. CONCLUSIONS: Our results suggest that the quantitative parameters obtained by advanced imaging methods may be useful in predicting the high proliferation in invasive breast carcinomas. But none of them is eligible to be used as an independent biomarker in distinguishing aggressive behavior. Nevertheless, as a noninvasive method, visual assessment of microvascular morphology using SMI increases the prognostic efficiency in invasive breast carcinomas.

Is there any additional benefit of 68Ga-PSMA PET on radiotherapy target volume definition in patients with glioblastoma?

OBJECTIVE: To investigate the contribution of 68Gallium (68Ga)-PSMA (prostate-specific membrane antigen) positron emission tomography (PET) in defining radiotherapy (RT) target volume for glioblastoma and to compare the target volumes defined by Magnetic Resonance Imaging (MRI). METHODS: RT planning Computed Tomography (CT) images were fused separately with pre-operative MRI and PET/MRI images of 10 glioblastoma patients, retrospectively. The contrast-enhanced area in T1 weighted MRI was contoured as gross tumor volume (GTV) and clinical target volume (CTV1) was obtained by including the cavity and T2/FLAIR hyperintense areas after giving a margin of 2 cm to the GTV. 68Ga-PSMA uptake area was contoured as biological tumor volume (BTV) and CTV2 was obtained with a margin of 2 cm to BTV. Planning target volumes (PTVs) were created with the 3 mm added to the CTVs. Conformity index (CI), dice similarity coefficient (DSC) and overlap volume (OV) were calculated by obtaining the intersection and union volumes. Volumetric comparison, similarity and overlap analyzes were performed statistically by Wilcoxon signed rank and One sample t-test. RESULTS: The median GTV was 21,96 cc (1,04 - 82,04) and BTV was 25,58 cc (2,43 - 99,47). BTV was on average 47% larger than GTV which was statistically significant (p = 0.03). For GTV-BTV, CTV1-CTV2 and PTV1-PTV2; mean values of CI were 0,56, 0,76 and 0,76; DSC were 0,70, 0,86 and 0,86; OV were 0,88, 0,94 and 0,94, respectively. There was no significant difference on size and spatial similarity between CTV1 and CTV2, PTV1 and PTV2. CONCLUSION: Altough BTV was larger than GTV, this significance was lost while we gave the same CTV margin including the peripheral edema. It seems that it may help to improve defining non-enhancing tumor part and also recurrent tumor volume. ADVANCES IN KNOWLEDGE: Recent studies have focused on the role of 68Ga-PSMA PET in imaging of glial tumors. It has been observed that 68Ga-PSMA PET can clearly define the tumor borders and it can be beneficial in target volume delineation, especially in reirradiation of recurrent tumors.

99mTc-Vitamin C SPECT/CT imaging in SARS-CoV-2 associated pneumonia.

We present the first 99mTc-Vitamin C single-photon emission computed tomography/computed tomography (SPECT/CT) images obtained in patients with SARS-CoV-2 (COVID-19) infection. The CT portion of SPECT/CT images showed mostly peripheral patchy and ground-glass opacities in both lungs, which are consistent with a diagnosis of SARS-CoV-2-associated pneumonia in both patients. 99mTc-Vitamin C SPECT images showed increased tracer uptake corresponding to abnormal lung findings seen on CT in patient 1 who was newly diagnosed and treatment naïve. However, no abnormal uptake corresponding to lung CT findings was seen in patient 2 who received anti-SARS-CoV-2 treatment.

Radiopharmaceutical for detecting PSMA - positive metastatic colon cancer: Matched-pair comparison of 18F-BF3-Cy3-ACUPA and 68Ga-PSMA PET/MRI.

Prostate-specific membrane antigen (PSMA) - based radiopharmaceuticals are promising for the evaluation of PSMA-positive non-prostate cancers. In this case study, 18F-BF3-Cy3-ACUPA and 68Ga-PSMA positron emission tomography/magnetic resonance imaging (PET/MRI) were compared in a patient with metastatic colon cancer. Both 18F-BF3-Cy3-ACUPA and 68Ga-PSMA PET/MRI showed biopsy-proven metastatic left external iliac adenopathy, highlighting the feasibility of PSMA uptake in PET/MRI of metastatic nodal disease from colon cancer. Along with imaging evaluation, PSMA-based radiopharmaceuticals may also be used as a surrogate imaging tracer for potential theranostic applications using alpha or beta emitters in the context of PSMA-directed radiopharmaceutical therapy in advanced and progressive colorectal cancer.

A case of hepatic focal nodular hyperplasia mimicking hepatocellular carcinoma identified on gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography.

Prostate-specific membrane antigen (PSMA) is a glycosylated type-II transmembrane protein highly expressed in individual tumor cells. Lesions with PSMA expression in the liver are commonly reported as prostate cancer metastasis or hepatocellular cancer previously. This is the first case reported as hepatic focal nodular hyperplasia, mimicking hepatocellular carcinoma with imaging features. This patient, having a lesion that has been enlarged from 2.0 cm to 2.5 cm in 3 months, was referred to our department for restaging by gallium-68 PSMA (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT). The CT scan showed a focal segment VI hypodensity, which was significantly PSMA-avid. Consequently, its biopsy resulted as focal nodular hyperplasia in liver. His follow-up 68Ga-PSMA PET/CT ultimately revealed a mass lesion of 8 cm of axial diameter.

225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient.

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient's baseline germline mutation likely predisposed him to more aggressive disease.

Evaluation of F-18 DOPA PET/CT in the detection of recurrent or metastatic medullary thyroid carcinoma: comparison with GA-68 DOTA-TATE PET/CT.

OBJECTIVE: PET imaging with F-18 DOPA (FDOPA) and Ga-68 DOTATATE (TATE) shows the most promising results to detect medullary thyroid cancer (MTC) recurrence. We performed this comparative study to detect the site of recurrent or metastatic disease in MTC patients with elevated serum calcitonin (Ctn) and/or carcinoembryonic antigen (CEA) levels. METHODS: We studied 46 MTC patients (25 women, 21 men) with elevated Ctn and/or CEA levels during follow-up who had both FDOPA and TATE PET/CT scans for re-staging purposes. RESULTS: FDOPA PET imaging yielded an overall sensitivity of 86.8%, specificity of 100%, PPV of 100%, NPV of 61.5%, and accuracy of 89.1%, while TATE PET scan had the same values as 84.2%, 87.5%, 96.9%, 53.8%, and 84.6%, respectively, and there was no statistically significant difference between the two modalities with the exception of the specificity value that was higher for FDOPA imaging. In a subgroup of patients with overt Ctn or CEA elevation, sensitivity of FDOPA increased significantly, whereas TATE sensitivity did not change. FDOPA PET imaging was significantly superior in detecting liver and regional lymph node (LN) metastases, while TATE PET scan was significantly better in the skeletal metastases. Early FDOPA demonstrated 11 invisible lesions on late FDOPA. CONCLUSION: Both FDOPA and TATE PET/CT imaging are useful to localize recurrences in MTC patients. While TATE imaging is superior to reveal skeletal disease, FDOPA seems better in liver and regional LN metastases; therefore, the two modalities appear complementary in monitoring MTC patients with elevated serum Ctn and/or CEA levels.

Transient minimal hydronephrosis on contralateral kidney in infants with unilateral hydronephrosis: Is it an early sign of worsening of the affected kidney?

Background/aim: The criteria for surgical management of ureteropelvic junction obstruction are not well-defined, and there is a risk for loss of renal function before the operation. In this context, certain changes in contralateral kidney had been investigated in order to increase the sensitivity of diagnosis. In this study, we aimed to investigate whether contralateral transient minimal hydronephrosis (CTMH) can be considered as an "early alarm" sign for worsening of the affected kidney in infants with hydronephrosis. Materials and methods: A total of 182 infants (92 surgically treated and 90 conservatively followed-up) with unilateral hydronephrosis were retrospectively analyzed. Ultrasonography and renal scan findings were evaluated. Correlation between the appearance of CTMH, contralateral compensatory hypertrophy (CCH) on ultrasonography, and prognosis of the affected kidney were evaluated. Results: Among the surgically treated patients, 18 (19.6%) patients developed CTMH on average 7 months (0­13 months) before surgery. Among these 18 patients with CTMH, 12 patients (66.6%) had loss of renal function preoperatively, while this ratio was 29.7% on their counterparts (p = 0049). CCH was observed in 31 (33.7%) individuals in surgically treated patient group including all 18 patients with CTMH, while none of the conservatively followed-up patients developed CCH and/or CTMH. In the multiple logistic regression analysis, among the variables investigated, CTMH was found as an independent predictor of the deterioration in the affected kidney and of the poor prognosis (p = 0.011 and p = 0.0004, respectively). Conclusion: In our study, among the variables investigated, CTMH was found as an independent predictor of the deterioration in the affected kidney and poor prognosis in infants followed-up with isolated unilateral hydronephrosis. Additionally, CTMH can be considered as an "early alarm" sign for worsening of the affected kidney and the need for surgical intervention.

Small Molecule, Multimodal, [18F]-PET and Fluorescence Imaging Agent Targeting Prostate-Specific Membrane Antigen: First-in-Human Study.

BACKGROUND: A first-in-human study of [18F]-BF3-Cy3-ACUPA, a small-molecule imaging agent that can be unimolecularly both positron emitting and fluorescent, is conducted to determine its safety, biodistribution, radiation dosimetry, feasibility in tumor detection by preoperative positron emission tomography (PET), as well as its intraoperative fluorescence imaging utility in patients with prostate-specific membrane antigen positive (PSMA+) tumors. METHODS: Ten patients aged 66 ± 7 years received a 6.5 ± 3.2 mCi intravenous injection of [18F]-BF3-Cy3-ACUPA and underwent PET/computed tomography (CT) imaging. Radiation dosimetry of [18F]-BF3-Cy3-ACUPA, normal organ biodistribution, and tumor uptakes were examined. Two patients were prescheduled for radical prostatectomy (RP) with extended pelvic lymphadenectomy approximately 24 hours following [18F]-BF3-Cy3-ACUPA injection and imaging. Without reinjection, intraoperative fluorescence imaging was performed on freshly excised tissue during RP. Frozen sections of excised tissue during RP were submitted for confirmatory histopathology and multiphoton fluorescence and brightfield microscopy. RESULTS: Absorbed doses by organs including the kidneys and salivary glands were similar to 68Ga-PSMA-11 imaging. [18F]-BF3-Cy3-ACUPA physiologic radiotracer accumulation and urinary/biliary excretion closely resembled the distribution of other published PSMA tracers including [18F]-JK-PSMA-7, [18F]-PSMA-1007, [18F]-DCFPyL, and [18F]-DCFBC. 19F-BF3-Cy3-ACUPA was retained in PSMA+ cancer tissues in patients for at least 24 hours, allowing for intraoperative fluorescence assessment of the prostate and of the embedded prostate cancer without contrast reinjection. After 24 hours, the imaging agent mostly decayed or cleared from the blood pool. Preoperative PET and fluorescence imaging findings were confirmed with final histopathology and multiphoton microscopy. CONCLUSION: Our first-in-human results demonstrate that [18F]-BF3-Cy3-ACUPA is safe and feasible in humans. Larger trials with this PET tracer are expected to further define its capabilities and its clinical role in the management of PSMA+ tumors, especially in prostate cancer.

One-Step, Rapid, 18F-19F Isotopic Exchange Radiolabeling of Difluoro-dioxaborinins: Substituent Effect on Stability and In Vivo Applications.

The ß-diketone moiety is commonly present in many anticancer drugs, antibiotics, and natural products. We describe a general method for radiolabeling ß-diketone-bearing molecules with fluoride-18. Radiolabeling was carried out via 18F-19F isotopic exchange on nonradioactive difluoro-dioxaborinins, which were generated by minimally modifying the ß-diketone as a difluoroborate. Radiochemistry was one-step, rapid (<10 min), and high-yielding (>80%) and proceeded at room temperature to accommodate the half-life of F-18 (t1/2 = 110 min). High molar activities (7.4 Ci/µmol) were achieved with relatively low starting activities (16.4 mCi). It was found that substituents affected both the solvolytic stability and fluorescence properties of difluoro-dioxaborinins. An F-18 radiolabeled difluoro-dioxaborinin probe that was simultaneously fluorescent showed sufficient stability for in vivo positron emission tomography (PET)/fluorescence imaging in mice, rabbits, and patients. These findings will guide the design of probes with specific PET/fluorescence properties; the development of new PET/fluorescence dual-modality reporters; and accurate in vivo tracking of ß-diketone molecules.

68Ga PSMA PET/MR in the differentiation of low and high grade gliomas: Is 68Ga PSMA PET/MRI useful to detect brain gliomas?

BACKGROUND: Magnetic resonance imaging (MRI) is the most important imaging modality in the diagnosis and follow-up of glial brain tumors. OBJECTIVE: The aim of our study is to determine the correlation between tumor grade, determined with postoperative pathological examination, and standard uptake value (SUV), a semi-quantitative parameter, in patients who underwent imaging 68Ga-PSMA with using PET/MR. MATERIAL-METHOD: Thirty-five out of 38 patients' images whose pathology was consistent with glial tumor, 42 lesions from separate anatomic localizations or with higher activity uptake than the rest of the tumor were evaluated. SUV values measured on PET images and grade relationship were evaluated based on each lesion while mitosis, Ki-67 were evaluated for each patient. RESULTS: Grade, Ki-67, mitosis, necrosis and SUVmax/mean/peak were found statistically significant with moderate/high correlation. The parameter with the highest correlation coefficient was mitosis. (For SUVmax r = 0.64, p = 0). When Grade II and III were considered as the first group and IV as the second group, the cutoff values were found to be 2.3 for SUVmax, 0.21 for SUVmean and 0.63 for SUVpeak. In the diagnosis of HGG, PET's sensitivity is higher than MRI but no statistically difference was found between specificities. CONCLUSION: 68Ga PSMA PET imaging is found to be particularly useful in differentiating Grade IV glial tumors from other grades. This finding is thought to be important in the differentiation the relapse with postoperative tissue changes, which is an important problem in the follow-up.

Simultaneous use of FDG-18 and 68Ga-citrate PET/CT for the differential diagnosis of sarcoidosis and malignant disease.

A 67-year-old male presented with cutaneous rash, lassitude and fatigue of three weeks. Personal history included psoriasis and sarcoidosis. Physical examination revealed macular rash on the anterior chest wall. Laboratory results were within normal limits. Chest X-ray showed normal findings. Pulmonary function tests demonstrated a mild obstructive pattern and a mild decrease in DLCO/VA. Thorax CT revealed two nodules in the right upper and middle lobe. 68Ga-citrate PET/CT did not demonstrate any active inflammatory reaction associated with sarcoidosis while 18F-FDG PET/CT revealed increased FDG uptake in the right middle lobe, upper division bronchus and in the left lower abdominal quadrant. Histopathologic examination of the colon biopsy was compatible with adenocarcinoma and bronchoscopic biopsy of the lung lesions revealed nonspecific granulomatous inflammation. BAL cytology was normal while BAL culture did not grow any pathologic organisms. Simultaneous use of 18F-FDG and 68Ga-citrate PET/CT was the hallmark for the final diagnosis in our patient. While FDG/PET has detected the pulmonary and colonic malignant foci in our patient, 68Ga-citrate PET/CT excluded the presence of active granulomatous inflammation of sarcoidosis. Simultaneous utility of these two imaging modalities in patients with sarcoidosis is of great importance in terms of guiding the clinician towards the accurate diagnostic pathway which is the hallmark for final diagnosis, especially in the presence of concomitant malignant disease.

Co-existence of multiple sclerosis and anti-NMDA receptor encephalitis: A case report and review of literature.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a serious autoimmune disorder characterized by psychiatric symptoms, seizures and movement disorder. Predisposing factors have been reported since the time it was described, and its pathophysiology has been tried to be clarified over the years. Although overlap with other demyelinating diseases had been reported, such an association between Multiple Sclerosis (MS) anti ANTI-NMDAR encephalitis is limited to only a few case reports. In this article, a patient diagnosed with relapsing remitting multiple sclerosis (RRMS) for ten years who then developed NMDA-R encephalitis while on disease modifying treatment will be presented and possible common pathophysiology with previously reported literature will be discussed.