Testicular metastasis of prostate adenocarcinoma: the other side of orchiepididymitis.

Background: Metastatic prostate adenocarcinoma is a rare event and there are few references to this topic. We report an unusual case of prostate cancer metastasis and review of contemporary literature. Moreover, we discuss the pathogenesis and the clinical aspects of this event. Case presentation: A 70-year-old patient was admitted to the hospital for right scrotal pain. The ultrasound examination described an increase in testicular size, suggesting the possibility of orchiepididymitis. Past medical history reported a previous prostate adenocarcinoma. Inflammatory blood tests were normal. Importantly, PSA was 3.3 ng/ml. PET scan positivity in the scrotum raised suspicion of a relapse. Therefore, he underwent right orchiectomy. Conclusion: Although metastatic prostate adenocarcinoma is rare, a correct diagnosis is of paramount importance because the therapy changes accordingly. Patients who complain of scrotal pain need to be examined accurately. Although the most common cause behind this symptom is infectious, the patient's past medical history should be reviewed to exclude previous malignancies.

Non-Hodgkin Lymphoma Developed Shortly after mRNA COVID-19 Vaccination: Report of a Case and Review of the Literature.

We report on a 66-year-old man who presented with a right axillary lymphadenopathy approximately 10 days after receiving the third dose of the BNT162b2 vaccine. The lymphadenopathy gradually enlarged, and physical examination and ultrasound (US) revealed one right axillary 6.99 cm and one right supraclavicular 2.36 cm lymphadenopathy. Histologic examination of the right axillary nodule revealed anaplastic large-cell lymphoma that was ALK negative and CD30 positive. A total body computerized tomography (CT) scan, positron emission tomography (PET) and bone-marrow biopsy showed a stage-II non-Hodgkin lymphoma (NHL). The patient was treated with chemotherapy and a scheme of Brentuximab Vedotin, Cyclophosphamide, Doxorubicin and Prednisone (BV-CHP) for six cycles and is now well and in complete remission. The revision of the literature revealed eight additional cases of NHL developed shortly after COVID-vaccination. There were four cases of diffuse large-B-cell lymphoma (DLBCL) (one in a patient who was a heart transplant recipient and developed an Epstein-Bar-virus-positive DLBCL), one case of extranodal NK/T-cell lymphoma, one patient with subcutaneous panniculitis-like T-cell lymphoma, one case of marginal zone B-cell lymphoma and one primary cutaneous anaplastic large-cell lymphoma (PC-ALCL). In five cases, the lymphoma developed after BNT162b2 mRNA vaccination, including one case after ChAdOx1 nCOV-19, one case after the adenovirus type 26 (Ad26) vaccine and one after mRNA-1273/Spikevax (ModernaTX). We are aware that the link between COVID-19 vaccination and lymphoma most likely is a chance phenomenon, and that COVID-19 vaccines represent very efficient products for many people around the world. However, we believe that clinical events, even if only temporally associated with novel treatments or novel vaccines, should be reported for the benefit of the patients and the scientific community.

A Specific HPLC Method to Determine Residual HEPES in [68Ga]Ga-Radiopharmaceuticals: Development and Validation.

Background: Nowadays, in Nuclear Medicine, clinically applied radiopharmaceuticals must meet quality release criteria such as high radiochemical purity and radiochemical yield. Many radiopharmaceuticals do not have marketing authorization and have no dedicated monograph within European Pharmacopeia (Ph. Eur.); therefore, general monographs on quality controls (QCs) have to be applied for clinical application. These criteria require standardization and validation in labeling and preparation, including quality controls measurements, according to well defined standard operation procedures. However, QC measurements are often based on detection techniques that are specific to a certain chromatographic system. Several radiosyntheses of [68Ga]Ga-radiopharmaceuticals are more efficient and robust when they are performed with 2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (HEPES) buffer, which is considered as an impurity to be assessed in the QC procedure, prior to clinical use. Thus, Ph. Eur. has introduced a thin-layer chromatography (TLC) method to quantify the HEPES amount that is present in [68Ga]Ga-radiopharmaceuticals. However, this is only qualitative and has proven to be unreliable. Here we develop and validate a new high-performance liquid chromatography (UV-Radio-HPLC) method to quantify the residual amount of HEPES in 68Ga-based radiopharmaceuticals. Method: To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document that was adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. A range of concentrations of HEPES (100, 80, 60, 40, 20, 10, 5, 3 µg/mL) were analyzed. Moreover, to test the validity and pertinence of our new HPLC method, we analyzed samples of [68Ga]Ga-DOTATOC; [68Ga]Ga-PSMA; [68Ga]Ga-DOTATATE; [68Ga]Ga-Pentixafor; and [68Ga]Ga-NODAGA-Exendin-4 from different batches that were prepared for clinical use. Results: In the assessed samples, HEPES could not be detected by the TLC method that was described in Ph. Eur. within 4 min incubation in an iodine-saturated chamber. Our developed HPLC method showed excellent linearity between 3 and 100 µg/mL for HEPES, with a correlation coefficient (R2) for calibration curves that was equal to 0.999, coefficients of variation (CV%) < 2%, and percent deviation value of bias from 100% to 5%, in accordance with acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed and the limit-of-quantification (LOQ) was 3 µg/mL, confirming the high sensitivity of the method. The amount of HEPES that was detected with our developed HPLC method in the tested [68Ga]Ga-radiopharmaceuticals resulted well below the Ph. Eur. limit, especially for [68Ga]Ga-NODAGA-Exendin-4. Conclusions: The TLC method that is described in Ph. Eur. to assess residual HEPES in [68Ga]-based radiopharmaceuticals may not be sufficiently sensitive and thus unsuitable for QC release. Our new HPLC method was sensitive, quantitative, reproducible, and rapid for QCs, allowing us to exactly determine the residual HEPES amount in [68Ga]Ga-radiopharmaceuticals for safe patient administration.

Development and Validation of an Analytical HPLC Method to Assess Chemical and Radiochemical Purity of [68Ga]Ga-NODAGA-Exendin-4 Produced by a Fully Automated Method.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in pancreatic islets, especially in ß-cells, and highly expressed in human insulinomas and gastrinomas. In recent years several GLP-1R-avid radioligands have been developed to image insulin-secreting tumors or to provide a tentative quantitative in vivo biomarker of pancreatic ß-cell mass. Exendin-4, a 39-amino acid peptide with high binding affinity to GLP-1R, has been labeled with Ga-68 for imaging with positron emission tomography (PET). Preparation conditions may influence the quality and in vivo behavior of tracers. Starting from a published synthesis and quality controls (QCs) procedure, we have developed and validated a new rapid and simple UV-Radio-HPLC method to test the chemical and radiochemical purity of [68Ga]Ga-NODAGA-exendin-4, to be used in the clinical routine. Methods: Ga-68 was obtained from a 68Ge/68Ga Generator (GalliaPharma®) and purified using a cationic-exchange cartridge on an automated synthesis module (Scintomics GRP®). NODAGA-exendin-4 contained in the reactor (10 µg) was reconstituted with HEPES and ascorbic acid. The reaction mixture was incubated at 100 °C. The product was purified through HLB cartridge, diluted, and sterilized. To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document released by the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human Use (ICH), adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. Therefore, a range of concentrations of Ga-NODAGA-exendin-4, NODAGA-exendin-4 (5, 4, 3.125, 1.25, 1, and 0.75 µg/mL) and [68Ga]Ga-NODAGA-exendin-4 were analyzed. To validate the entire production process, three consecutive batches of [68Ga]Ga-NODAGA-exendin-4 were tested. Results: Excellent linearity was found between 5-0.75 µg/mL for both the analytes (NODAGA-exendin-4 and 68Ga-NODAGA-exendin-4), with a correlation coefficient (R2) for calibration curves equal to 0.999, average coefficients of variation (CV%) < 2% (0.45% and 0.39%) and average per cent deviation value of bias from 100%, of 0.06% and 0.04%, respectively. The calibration curve for the determination of [68Ga]Ga-NODAGA-exendin-4 was linear with a R2 of 0.993 and CV% < 2% (1.97%), in accordance to acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed using 10 µg of peptide. The mean radiochemical yield was 45 ± 2.4% in all the three validation batches of [68Ga]Ga-NODAGA-exendin-4. The radiochemical purity of [68Ga]Ga-NODAGA-exendin-4 was >95% (97.05%, 95.75% and 96.15%) in all the three batches. Conclusions: The developed UV-Radio-HPLC method to assess the radiochemical and chemical purity of [68Ga]Ga-NODAGA-exendin-4 is rapid, accurate and reproducible like its fully automated production. It allows the routine use of this PET tracer as a diagnostic tool for PET imaging of GLP-1R expression in vivo, ensuring patient safety.

Prevalence of interstitial pneumonia suggestive of COVID-19 at 18F-FDG PET/CT in oncological asymptomatic patients in a high prevalence country during pandemic period: a national multi-centric retrospective study.

PURPOSE: To assess the presence and pattern of incidental interstitial lung alterations suspicious of COVID-19 on fluorine-18-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) ([18F]FDG PET/CT) in asymptomatic oncological patients during the period of active COVID-19 in a country with high prevalence of the virus. METHODS: This is a multi-center retrospective observational study involving 59 Italian centers. We retrospectively reviewed the prevalence of interstitial pneumonia detected during the COVID period (between March 16 and 27, 2020) and compared to a pre-COVID period (January-February 2020) and a control time (in 2019). The diagnosis of interstitial pneumonia was done considering lung alterations of CT of PET. RESULTS: Overall, [18F]FDG PET/CT was performed on 4008 patients in the COVID period, 19,267 in the pre-COVID period, and 5513 in the control period. The rate of interstitial pneumonia suspicious for COVID-19 was significantly higher during the COVID period (7.1%) compared with that found in the pre-COVID (5.35%) and control periods (5.15%) (p < 0.001). Instead, no significant difference among pre-COVID and control periods was present. The prevalence of interstitial pneumonia detected at PET/CT was directly associated with geographic virus diffusion, with the higher rate in Northern Italy. Among 284 interstitial pneumonia detected during COVID period, 169 (59%) were FDG-avid (average SUVmax of 4.1). CONCLUSIONS: A significant increase of interstitial pneumonia incidentally detected with [18F]FDG PET/CT has been demonstrated during the COVID-19 pandemic. A majority of interstitial pneumonia were FDG-avid. Our results underlined the importance of paying attention to incidental CT findings of pneumonia detected at PET/CT, and these reports might help to recognize early COVID-19 cases guiding the subsequent management.

Concomitant Primary Hyperparathyroidism in Patients with Multiple Myeloma: A Possible Link?

Hypercalcemia is a significant feature of patients with active multiple myeloma (MM) with extensive bone disease. Among the causes of non-neoplastic hypercalcemia, primary hyperparathyroidism (PHPT) is one of the most common, leading to osteoporosis and bone fractures. Interestingly, some preclinical data indicate that high secretion of parathyroid hormone (PTH) may have a negative impact on bone disease and MM progression. However, concomitant diagnosis of MM and PHPT has rarely been described. Here, we present 4 cases of patients with active MM and hypercalcemia with high or inappropriately normal PTH levels. Interestingly, CD138+ cells from these 4 MM patients lack PTH receptor 1 and PTH-related peptide expressions, indicating that PTH could have a paracrine rather than a direct pro-tumoral effect. Moreover, these cases suggest that the concomitant diagnosis of MM and PHTP may not be so rare and should be considered for the clinical management of MM patients with hypercalcemia.

Relationship between comprehensive geriatric assessment and amyloid PET in older persons with MCI.

BACKGROUND: The association between amyloid deposition and cognitive, behavioral and physical performance in mild cognitive impairment (MCI) due to Alzheimer's disease (AD) has been poorly investigated, especially in older persons. METHODS: We studied the in vivo correlation between the amyloid deposition at Positron Emission Tomography (amyloid-PET) and the presence of memory loss, reduced executive function, neuropsychiatric symptoms and physical performance in older persons with MCI. Amyloid-PET was performed with 18F-flutemetamol and quantitatively analyzed. RESULTS: We evaluated 48 subjects, 21 men and 27 women. We performed in each patient a comprehensive geriatric assessment (CGA) including Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), Activity Daily Living (ADL), Instrumental Activity of Daily Living (IADL), Neuropsychiatric inventory (NPI) questionnaire, 15 Geriatric Depression Scale (GDS), Short Physical Performance Battery (SPPB) and Hand Grip strength. Then, each patient underwent amyloid-PET. Mean age of the enrolled subjects was 74.6 ± 7.8 years. All of these subjects showed preserved cognitive function at MMSE > 24, while 29 of 48 subjects (61.0%) had altered CDT. Mean NPI score was 6.9 ± 5.9. The mean value of SPPB score was 9.0 ± 2.6, while the average muscle strength of the upper extremities measured by hand grip was 25.6 ± 7.7 Kg. CT/MRI images showed cortical atrophic changes in 26 of the 48 examined subjects (54.0%), while cerebrovascular modifications were present in 31 subjects (64.5%). Pathological burden of amyloid deposits was detected in 25 of 48 (52.0%) patients with a mean value of global z-score of 2.8 (subjects defined as MCI due to AD). After stratifying subjects in subclasses of clinical alterations, more probability of pathological amyloid deposition was found in subjects with impaired CDT and higher NPI score (O.R. = 3.45 [1.01-11.2], p = 0.04), with both impaired CDT and low physical performance (O.R. = 5.80 [1.04-32.2], p = 0.04), with altered CDT and high NPI score (O.R. = 7.98 [1.38-46.0], p = 0.02), and finally in those subjects with altered CDT, high NPI and low physical performance (O.R. = 5.80 [1.05-32.2], p = 0.04). CONCLUSION: Our findings support the recent hypothesis that amyloid deposition could be associated with multiple cerebral dysfunction, mainly affecting executive, behavioral and motor abilities.

Radiotherapy for the treatment of distant nodes metastases from oligometastatic urothelial cancer: A retrospective case series.

OBJECTIVES: To investigate the efficacy of stereotactic body radiotherapy in oligometastatic urothelial carcinoma with node-only involvement. METHODS: We retrospectively collected data on the outcomes of patients who underwent stereotactic body radiotherapy for metastatic node lesions from oligometastatic urothelial carcinoma at Radiotherapy Unit of University Hospital of Parma, Parma, Italy. The investigated outcomes were lesion size, standardized uptake value, overall response rate, lesion control rate, lesion progression-free interval, progression-free survival and overall survival. RESULTS: Among seven patients included in the study, a total of 14 node metastatic lesions were treated with stereotactic body radiotherapy. The mean total dose of stereotactic body radiotherapy was 32 Gy (range 25-40 Gy). At first imaging evaluation, a mean variation of -4% (P = 0.427) in major diameter, -16% (P = 0.048) in minor diameter and -76% in standardized uptake value (P < 0.001) were documented. The overall response rate and lesion control rate were 43% and 100%, respectively. Median lesion progression-free interval, progression-free survival and overall survival were 11.4 months (95% CI 3.4-19.4), 2.9 months (95% CI 2.6-3.1) and 14.9 months (95% CI 12.3-17.5), respectively. Stereotactic body radiotherapy was effective in delaying the beginning of a systemic chemotherapy in four patients. CONCLUSIONS: The present findings generate the hypothesis of a possible role for the use of stereotactic body radiotherapy in selected patients with distant node metastases from oligometastatic urothelial carcinoma.

Influence of dipyridamole stress echocardiography on galectin-3, amino-terminal B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T.

OBJECTIVE: Non-invasive assessment using a pharmacological provocative test is an essential part of the workup of patients admitted to the emergency department with chest pain. Some doubts, however, remain about the safety of dipyridamole stress echocardiography in patients with non-diagnostic troponin and ECG. METHODS AND RESULTS: Twenty-nine consecutive patients admitted to the emergency department with chest pain and no evidence of acute coronary syndrome were subjected to standard dipyridamole stress echocardiography. Blood samples for measurement of galectin-3, NT-proBNP and high-sensitivity troponin T (HS-TnT) were collected at the baseline and after provocative testing. The provocative test was positive in 7/29 patients. As compared with baseline measurements, no significant differences were observed in 1-h values of HS-TnT (10.7 versus 10.5 ng/L; P = 0.085) and galectin-3 (14.3 versus 13.7 ng/mL; P = 0.128), whereas values of NT-proBNP were slightly higher (126 versus 111 ng/L; P = 0.002). The 1-h delta variation of patients with a positive provocative test was significantly higher than that of patients with negative provocative testing for galectin-3 (1.12 versus 1.00; P < 0.001), but not for HS-TnT (0.98 versus 1.00; P = 0.184) and NT-proBNP (1.10 versus 1.04; P = 0.344). The 1-h delta variation of galectin-3 was > 1 in all patients with a positive provocative test as compared with 50% of patients with a negative provocative test (P = 0.018). CONCLUSIONS: Dipyridamole stress testing did not trigger clinically meaningful injuries to the myocardium. Galectin-3 testing may hence be preliminarily regarded as a complementary means for enhancing the diagnostic value of provocative testing. It is also worthwhile investigating whether patients with abnormal response to a provocative test and increased galectin-3 values may be targeted with specific therapy.

Computed tomography coronary angiography in patients with acute myocardial infarction without significant coronary stenosis.

BACKGROUND: It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients. METHODS AND RESULTS: Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified (P=0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm(2) versus 4.2±2.1 mm(2); P=0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P=0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P=0.01). CONCLUSIONS: CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.

Physical characterization of a new CT iterative reconstruction method operating in sinogram space.

Recently a new iterative reconstruction algorithm named Iterative Reconstruction (SAFIRE) has been released by Siemens. This algorithm works in the raw data domain with noise reduction as main purpose, providing five different strengths. In this study, the effect of SAFIRE on image quality has been investigated using selected phantoms and a comparison with standard filtered back projection (FBP) has been carried out. The following quantitative parameters have been evaluated: image noise, impact of different reconstruction kernels on noise reduction, noise power spectrum (NPS), contrast-to-noise ratio (CNR), spatial resolution, and linearity and accuracy of CT numbers. The influence of strengths on image quality parameters has also been examined. Results show that image noise reduction is independent of reconstruction kernel and strongly related to the strength of SAFIRE applied. The peak of NPS curve for SAFIRE reconstructions is shifted towards low frequencies; this effect is more marked at higher levels of strength. Contrast-to-noise ratio is always improved in SAFIRE reconstruction and increases with higher strength. At different dose levels SAFIRE preserves CT number accuracy, linearity, and spatial resolution, both in transversal and coronal planes. These results confirm that SAFIRE allows for image noise reduction with preserved image quality. First clinical data to validate this phantom analysis and confirm that commercially available iterative algorithms can play an effective role in dose containment.

Scale down and optimized automated production of [68Ga]68Ga-DOTA-ECL1i PET tracer targeting CCR2 expression.

BACKGROUND: Recently it has been identified a short peptide that showed allosteric antagonism against C-C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-D-amino acid peptidic CCR2 inhibitor called extracellular loop 1 inverso (ECL1i), d(LGTFLKC) has been identified and labeled to obtain a new probe for positron emission tomography in pulmonary fibrosis, heart injury, abdominal aortic aneurysm inflammation, atherosclerosis, head and neck cancer. Our goal was to develop, optimize and validate an automated synthesis method for [68Ga]68Ga-DOTA-ECL1i to make it available for a broader community. The synthesis of [68Ga]68Ga-DOTA-ECL1i was done using the Scintomics GRP® module with the already estabilished synthesis template for [68Ga]68Ga-DOTATOC/[68Ga]68Ga-PSMA. The radiopharmaceutical production was optimized scaling down the amount of DOTA-ECL1i (from 50 to 10 µg), evaluating synthesis efficiency and relevant quality control parameters in accordance with the European Pharmacopeia. RESULTS: Best results were yielded with 20 µg DOTA-ECL1i and then the process validation was carried out by producing three different batches on three different days obtaining an optimal radiochemical yield (66.69%) as well as radiochemical purity (100%) and molar activity (45.41 GBq/µmol). CONCLUSIONS: [68Ga]68Ga-DOTA-ECL1i was successfully synthesized and it is, thus, available for multi-dose application in clinical settings.

Validation of the HPLC Analytical Method for the Determination of Chemical and Radiochemical Purity of Ga-68-DOTATATE.

Purpose of the Study: Ga-68-DOTA-peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumors imaging using positron emission tomography (PET). A new selective and sensitive high-pressure liquid chromatography (HPLC) method was developed for determining chemical and radiochemical purity of Ga-68-DOTATATE (PET) tracer. The identification of peaks was achieved on a symmetry C18 column 3 µm 120Å (3.0 mm × 150 mm spherical particles) using (A) water + 0.1% trifluoroacetic acid (TFA) and (B) acetonitrile + 0.1% TFA, as the mobile phases at a flow rate of 0.600 mL/min and monitored at 220 nm. The run time was 16 min. Materials and Methods: The method was validated to fulfill International Conference on Harmonization requirements and EDQM guidelines, and it included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision. Results: The calibration curve was linear over the concentration range from 0.5 to 3 µg/ml, with a correlation coefficient (r2) equal to 0.999, average coefficient of variation (CV%) 2%, and average bias% did not deviate more than 5% for all concentrations. The LOD and LOQ for DOTATATE were 0.5 and 0.1 µg/mL, respectively. The method was considered precise, obtaining coefficients of variation between 0.22% and 0.52% for intraday and 0.20% and 0.61% for interday precision. Accuracy of method was confirmed with average bias% that did not deviate more than 5% for all concentrations. Conclusion: All results were acceptable and this confirmed that the method is suitable for its intended use in routine quality control of Ga-68-DOTATATE to guarantee the high quality of the finished product before release.

High Prognostic Value of 68Ga-PSMA PET/CT in Renal Cell Carcinoma and Association with PSMA Expression Assessed by Immunohistochemistry.

In oligo-metastatic renal cell carcinoma (RCC), neither computed tomography (CT) nor bone scan is sensitive enough to detect small tumor deposits hampering early treatment and potential cure. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein expressed in the neo-vasculature of numerous malignant neoplasms, including RCC, that can be targeted by positron emission tomography (PET) using PSMA-targeting radioligands. Our aim was to investigate whether PSMA-expression patterns of renal cancer in the primary tumor or metastatic lesions on immunohistochemistry (IHC) are associated with PET/CT findings using [68Ga]-PSMA-HBED-CC (PSMA-PET/CT). We then analyzed the predictive and prognostic role of the PSMA-PET/CT signal. In this retrospective single-center study we included patients with renal cancer submitted to PSMA-PET/CT for staging or restaging, with tumor specimens available for PSMA-IHC. Clinical information (age, tumor type, and grade) and IHC results from the primary tumor or metastases were collected. The intensity of PSMA expression at IHC was scored into four categories: 0: none; 1: weak; 2: moderate; 3: strong. PSMA expression was also graded according to the proportion of vessels involved (PSMA%) into four categories: 0: none; 1: 1-25%; 2: 25-50%; 3: >50%. The intensity of PSMA expression and PSMA% were combined in a three-grade score: 0-2 absent or mildly positive, 3-4 moderately positive, and 5-6 strongly positive. PSMA scores were used for correlation with PSMA-PET/CT results. Results: IHC and PET scans were available for the analysis in 26 patients (22 ccRCC, 2 papillary RCC, 1 chromophobe, 1 "not otherwise specified" RCC). PSMA-PET/CT was positive in 17 (65%) and negative in 9 patients (35%). The mean and median SUVmax in the target lesion were 34.1 and 24.9, respectively. Reporter agreement was very high for both distant metastasis location and local recurrence (kappa 1, 100%). PSMA-PET detected more lesions than conventional imaging and revealed unknown metastases in 4 patients. Bone involvement, extension, and lesion number were greater than in the CT scan (median lesion number on PET/CT 3.5). The IHC PSMA score was concordant in primary tumors and metastases. All positive PSMA-PET/CT results (15/22 ccRCC, 1 papillary cancer type II, and 1 chromofobe type) were revealed in tumors with strong or moderate PSMA combined scores (3-4 and 5-6). In ccRCC tissue samples, PSMA expression was strong to moderate in 20/22 cases. The SUVmax values correlated to the intensity of PSMA expression which were assessed using IHC (p = 0.01), especially in the ccRCC subgroup (p = 0.009). Median survival was significantly higher in patients with negative PSMA-PET/CT (48 months) compared to patients with a positive scan (24 months, p= 0.001). SUVmax ≥ 7.4 provides discrimination of patients with a poor prognosis. Results of PSMA-PET/CT changed treatment planning. Conclusions: in renal cancer, positive PSMA-PET/CT is strongly correlated to the intensity of PSMA expression on immunohistochemistry in both ccRCC and chromophobe cancer. PSMA-PET/CT signal predicts a poor prognosis confirming its potential as an aggressiveness biomarker and providing paramount additional information influencing patient management.

Lymph node staging with 68Ga-PSMA PET in patients with intermediate and high-risk prostate cancer suitable for radical prostatectomy managed in a prostate cancer unit.

BACKGROUND: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is coming up as a superior imaging tool for prostate cancer (PCa). However, its use in primary staging is still debated. The aim of this study was to assess accuracy of 68Ga-PSMA PET/CT in staging patients with intermediate and high risk PCa candidates to radical prostatectomy managed in the Prostate Cancer Unit of our institution. METHODS: We retrospectively evaluated patients with biopsy-proven PCa staged through PSMA PET/CT before undergoing radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND). PET findings were categorized with respect to primary tumor (T), nodal (N) and distant metastasis (M). We analyzed the correspondence between PSMA PET/CT and final histopathological examination. RESULTS: We evaluated 42 men with high and intermediate risk PCa submitted to RP with ePLND. Mean age was 65.5 years (range, 49-76 years) and median preoperative prostate-specific antigen (PSA) was 13 ng/mL (IQR, 8.1-20 ng/mL). Patients in the high-risk group were 23 (54.7%), and the remainders were in the intermediate risk group. The mean risk of lymph node involvement (LNI) using the Memorial Sloan Kettering Cancer Center (MSKCC)-nomogram was 20%. The most common International Society of Urological Pathology (ISUP) grade was 3 (26.19%) after prostate biopsy. PSMA PET/CT showed focal prostatic uptake in 28 patients [mean value of maximum standardized uptake value (SUVmax) 18.5] and detected pelvic lymph node metastases in 6 cases (14.3%) with a median value of SUVmax 4.5 (IQR, 2-6.9). Histopathological examination detected lymph node metastases in seven patients (16.6%). In the only patient with negative PSMA PET/CT pathology revealed the presence of micrometastasis. After histopathological confirmation, sensitivity, specificity, positive and negative predictive values of pre-operative 68Ga-PSMA PET/CT were 85.7%, 100%, 100% and 97%, respectively. CONCLUSIONS: In our series, 68Ga-PSMA PET/CT holds high overall diagnostic value for lymph node staging in patients with intermediate and high risk PCa. Accuracy may depend on lymph node size.

Predicting amyloid-PET status in a memory clinic: The role of the novel antero-posterior index and visual rating scales.

INTRODUCTION: Visual rating scales are increasingly utilized in clinical practice to assess atrophy in crucial brain regions among patients with cognitive disorders. However, their capacity to predict Alzheimer's disease (AD)-related pathology remains unexplored, particularly within a heterogeneous memory clinic population. This study aims to assess the accuracy of a novel visual rating assessment, the antero-posterior index (API) scale, in predicting amyloid-PET status. Furthermore, the study seeks to determine the optimal cohort-based cutoffs for the medial temporal atrophy (MTA) and parietal atrophy (PA) scales and to integrate the main visual rating scores into a predictive model. METHODS: We conducted a retrospective analysis of brain MRI and high-resolution TC scans from 153 patients with cognitive disorders who had undergone amyloid-PET assessments due to suspected AD pathology in a real-world memory clinic setting. RESULTS: The API scale (cutoff ≥1) exhibited the highest accuracy (AUC = 0.721) among the visual rating scales. The combination of the cohort-based MTA and PA threshold with the API yielded favorable accuracy (AUC = 0.787). Analyzing a cohort of MCI/Mild dementia patients below 75 years of age, the API scale and the predictive model improved their accuracy (AUC = 0.741 and 0.813, respectively), achieving excellent results in the early-onset population (AUC = 0.857 and 0.949, respectively). CONCLUSION: Our study emphasizes the significance of visual rating scales in predicting amyloid-PET positivity within a real-world memory clinic. Implementing the novel API scale, alongside our cohort-based MTA and PA thresholds, has the potential to substantially enhance diagnostic accuracy.

ITA-IMMUNO-PET: The Role of [18F]FDG PET/CT for Assessing Response to Immunotherapy in Patients with Some Solid Tumors.

AIM: To examine the role of [18F]FDG PET/CT for assessing response to immunotherapy in patients with some solid tumors. METHODS: Data recorded in a multicenter (n = 17), retrospective database between March and November 2021 were analyzed. The sample included patients with a confirmed diagnosis of a solid tumor who underwent serial [18F]FDG PET/CT (before and after one or more cycles of immunotherapy), who were >18 years of age, and had a follow-up of at least 12 months after their first PET/CT scan. Patients enrolled in clinical trials or without a confirmed diagnosis of cancer were excluded. The authors classified cases as having a complete or partial metabolic response to immunotherapy, or stable or progressive metabolic disease, based on a visual and semiquantitative analysis according to the EORTC criteria. Clinical response to immunotherapy was assessed at much the same time points as the serial PET scans, and both the obtained responses were compared. RESULTS: The study concerned 311 patients (median age: 67; range: 31-89 years) in all. The most common neoplasm was lung cancer (56.9%), followed by malignant melanoma (32.5%). Nivolumab was administered in 46.3%, and pembrolizumab in 40.5% of patients. Baseline PET and a first PET scan performed at a median 3 months after starting immunotherapy were available for all 311 patients, while subsequent PET scans were obtained after a median 6, 12, 16, and 21 months for 199 (64%), 102 (33%), 46 (15%), and 23 (7%) patients, respectively. Clinical response to therapy was recorded at around the same time points after starting immunotherapy for 252 (81%), 173 (56%), 85 (27%), 40 (13%), and 22 (7%) patients, respectively. After a median 18 (1-137) months, 113 (36.3%) patients had died. On Kaplan-Meier analysis, metabolic responders on the first two serial PET scans showed a better prognosis than non-responders, while clinical response became prognostically informative from the second assessment after starting immunotherapy onwards. CONCLUSIONS: [18F]FDG PET/CT could have a role in the assessment of response to immunotherapy in patients with some solid tumors. It can provide prognostic information and thus contribute to a patient's appropriate treatment. Prospective randomized controlled trials are mandatory.

Can Baseline [18F]FDG PET/CT Predict Response to Immunotherapy After 6 Months and Overall Survival in Patients with Lung Cancer or Malignant Melanoma? A Multicenter Retrospective Study.

Aim: To assess the role of baseline 18F-fluorodeoxyglucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in predicting response to immunotherapy after 6 months and overall survival (OS) in patients with lung cancer (LC) or malignant melanoma (MM). Materials and Methods: Data from a multicenter, retrospective study conducted between March and November 2021 were analyzed. Patients >18 years old with a confirmed diagnosis of LC or MM, who underwent a baseline [18F]FDG-PET/CT within 1-2 months before starting immunotherapy and had a follow-up of at least 12 months were included. PET scans were examined visually and semiquantitatively by physicians at peripheral centers. The metabolic tumor burden (number of lesions with [18F]FDG-uptake) and other parameters were recorded. Clinical response was assessed at 3 and 6 months after starting immunotherapy, and OS was calculated as the time elapsing between the PET scan and death or latest follow-up. Results: The study concerned 177 patients with LC and 101 with MM. Baseline PET/CT was positive in primary or local recurrent lesions in 78.5% and 9.9% of cases, in local/distant lymph nodes in 71.8% and 36.6%, in distant metastases in 58.8% and 84%, respectively, in LC and in MM patients. Among patients with LC, [18F]FDG-uptake in primary/recurrent lung lesions was more often associated with no clinical response to immunotherapy after 6 months than in cases without any tracer uptake. After a mean 21 months, 46.5% of patients with LC and 37.1% with MM had died. A significant correlation emerged between the site/number of [18F]FDG foci and death among patients with LC, but not among those with MM. Conclusions: In patients with LC who are candidates for immunotherapy, baseline [18F]FDG-PET/CT can help to predict response to this therapy after 6 months, and to identify those with a poor prognosis based on their metabolic parameters. For patients with MM, there was only a weak correlation between baseline PET/CT parameters, response to therapy, and survival.

Progressive Unspecified Motor Speech Disorder: A Longitudinal Single Case Study of an Older Subject.

INTRODUCTION: In a few cases, neurodegenerative diseases debut with a speech disorder whose differential diagnosis can be difficult. CASE REPORT: We describe the case of a right-handed woman with a progressive speech impairment, which debuted when she was 80 years old. We report the results of neurological, neuropsychological, and imaging assessments with positron emission tomography (PET) over a period of nine years. Metabolic PET with 18F-FDG was performed at the age of 81 and repeated two years later due to the worsening of symptoms; amyloid PET with 18F-flutemetamol was performed at the age of 86. All PET results were quantitatively analyzed. A speech impairment remained the isolated neurological symptom for a long time, together with a mood disorder. Early FDG-PET showed hypometabolism in the left superior and inferior frontal areas, in the left superior temporal area, and in the right superior frontal area. Two years later, the hypometabolic area was more extensive. Amyloid PET was qualitatively and quantitatively normal. Nine years after the first symptoms, the speech production progressively worsened until complete anarthria, in association with writing impairment onset and signs of behavioral impairments. No signs of motor involvement were found. CONCLUSIONS: A progressive articulatory disorder without an evolution of motor disorders may be a distinct neurological degenerative entity, mainly affecting speech production for very a long time and with a specific early metabolic pattern in brain FDG-PET in the language production area. Monitoring patients with FDG-PET could predict the disease evolution years before a clinical deterioration.