Rationale for Prostate-Specific-Membrane-Antigen-Targeted Radionuclide Theranostic Applied to Metastatic Clear Cell Renal Carcinoma.

Prostate-specific membrane antigen (PSMA), whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma, is also highly expressed in the neovessels of various solid tumors, including clear cell renal cell carcinoma (ccRCC). In the VISION phase III clinical trial, PSMA-targeted radioligand therapy (PRLT) with lutetium 177 demonstrated a 4-month overall survival OS benefit compared to the best standard of care in heavily pretreated metastatic prostate cancer. Despite the improvement in the management of metastatic clear cell renal cell carcinoma (mccRCC) with antiangiogenic tyrosine kinase inhibitor (TKI) and immunotherapy, there is still a need for new treatments for patients who progress despite these drugs. In this study, we discuss the rationale of PRLT applied to the treavtment of mccRCC.

Discriminating Inflammatory Radiation-Related Changes From Early Recurrence in Patients With Glioblastomas: A Preliminary Analysis of 68 Ga-PSMA-11 PET/CT Compared With 18 F-FDOPA PET/CT.

PURPOSE OF THE REPORT: Using morphological and functional imaging to discriminate recurrence from postradiation-related modifications in patients with glioblastomas remains challenging. This pilot study aimed to assess the feasibility of using 68 Ga-prostate-specific membrane antigen (PSMA) 11 PET/CT compared with 18 F-FDOPA PET/CT to detect early recurrence. METHODS: Nine patients followed up for glioblastomas who received MRI during 12 months of follow-up were referred for both 68 Ga-PSMA-11 and 18 F-FDOPA PET/CT. The SUV max , lesion-to-striatum ratio, lesion-to-normal parenchyma ratio, and lesion-to-salivary gland ratio were calculated. RESULTS: Good correlation between 18 F-FDOPA and 68 Ga-PSMA PET/CT findings was seen in 5 patients. In 4 patients, the findings of both examinations were consistent with recurrence but were better visualized with the PSMA PET/CT. Examinations of the fifth patient were suggestive of postradiation-related changes and were better analyzed with the PSMA PET/CT, which displayed relatively low uptake compared with DOPA PET/CT. Conversely, 4 patients showed conflicting results: recurrence was not detected on the PSMA PET/CT because of previously introduced bevacizumab treatment; in another patient, both examinations were consistent with recurrence, but there was an uptake mismatch at the suspected lesion sites, and 2 patients presented with inconsistent findings. CONCLUSIONS: Despite a few discrepancies, this study highlights the potential role of 68 Ga-PSMA-11 PET/CT for discriminating postradiation inflammation from recurrence. 68 Ga-PSMA-11 PET/CT has an excellent lesion-to-background ratio, and false-positive and false-negative results could be minimized through implementing certain protocols before performing the examination. More powerful prospective studies are required to validate our results.

Yttrium-90 quantitative phantom study using digital photon counting PET.

BACKGROUND: PET imaging of 90Y-microsphere distribution following radioembolisation is challenging due to the count-starved statistics from the low branching ratio of e+/e- pair production during 90Y decay. PET systems using silicon photo-multipliers have shown better 90Y image quality compared to conventional photo-multiplier tubes. The main goal of the present study was to evaluate reconstruction parameters for different phantom configurations and varying listmode acquisition lengths to improve quantitative accuracy in 90Y dosimetry, using digital photon counting PET/CT. METHODS: Quantitative PET and dosimetry accuracy were evaluated using two uniform cylindrical phantoms specific for PET calibration validation. A third body phantom with a 9:1 hot sphere-to-background ratio was scanned at different activity concentrations of 90Y. Reconstructions were performed using OSEM algorithm with varying parameters. Time-of-flight and point-spread function modellings were included in all reconstructions. Absorbed dose calculations were carried out using voxel S-values convolution and were compared to reference Monte Carlo simulations. Dose-volume histograms and root-mean-square deviations were used to evaluate reconstruction parameter sets. Using listmode data, phantom and patient datasets were rebinned into various lengths of time to assess the influence of count statistics on the calculation of absorbed dose. Comparisons between the local energy deposition method and the absorbed dose calculations were performed. RESULTS: Using a 2-mm full width at half maximum post-reconstruction Gaussian filter, the dosimetric accuracy was found to be similar to that found with no filter applied but also reduced noise. Larger filter sizes should not be used. An acquisition length of more than 10 min/bed reduces image noise but has no significant impact in the quantification of phantom or patient data for the digital photon counting PET. 3 iterations with 10 subsets were found suitable for large spheres whereas 1 iteration with 30 subsets could improve dosimetry for smaller spheres. CONCLUSION: The best choice of the combination of iterations and subsets depends on the size of the spheres. However, one should be careful on this choice, depending on the imaging conditions and setup. This study can be useful in this choice for future studies for more accurate 90Y post-dosimetry using a digital photon counting PET/CT.

Optimization of the radiosynthesis of [68Ga]Ga-PSMA-11 using a Trasis MiniAiO synthesizer: do we need to heat and purify?

INTRODUTION:: [Ga]Ga-prostate specific membrane antigen (PSMA)-11 showed a clear gain in sensitivity for lesion detection in the biological recurrence of prostate cancer as compared to the standard [F]fluorocholine radiopharmaceutical. To meet the strong demand for [Ga]Ga-PSMA-11, we aimed to optimize an automated radiolabeling process by evaluating the influence of different key parameters on radiochemical purity and radiochemical yield. METHODS: The radiosynthesis of [Ga]Ga PSMA-11 was performed using a Trasis MiniAio synthesizer and a Ge/Ga GalliaPharm generator supplied by Eckert & Ziegler, Berlin, Germany. Optimized labeling parameters were evaluated by variation of sodium acetate concentrations and temperature of radiolabeling as well as the purification process. RESULTS: For each condition tested, radiochemical purity was higher than 99% in the final vial without batch failure, indicating a robust and fast radiosynthesis process. Radiosynthesis without the solid phase extraction purification process at room temperature in less than 5 min resulted in a radiolabeling efficiency of over 99% and remained stable at least 4 h without manual processing to limit operator radiation exposure. CONCLUSION: The procedure was completely automated and provided a high radiochemical yield. It can be performed several times a day, facilitating the clinical demand of this radiopharmaceutical.

Time in Therapeutic Range of Oral Vitamin K Antagonists in Hospitalized Elderly Patients.

BACKGROUND: Oral vitamin K antagonists (VKAs) are commonly used in older adults. To ensure the efficiency and safety of these drugs, the international normalized ratio (INR) must be monitored. The time in therapeutic range (TTR) is an internationally recommended assessment of the anticoagulation quality. OBJECTIVE: Our study aimed to assess the TTR of VKAs in a hospitalized geriatric population and identify factors associated with low TTR. METHODS: This was a multicenter retrospective study of data from 1899 patients with a mean age of 87 years between 2013 and 2015 in the geriatric units of four French hospitals. The data collection consisted of 2450 VKA prescriptions. We excluded prescriptions with a duration of < 7 days, monitoring with fewer than two INR values and patients with prosthetic heart valves. TTR was assessed using the Rosendaal method. Factors associated with a low TTR (< 50%) were assessed using a non-parametric method. RESULTS: The mean TTR observed in this population was 42.6%. The TTR was < 50% for 62.5% of the patients included in this study. Significant associations were found between TTR < 50% and aspartate transaminase (AST), alkaline phosphatase (ALT), thyroid-stimulating hormone (TSH), prescription duration, fluconazole instauration, hemoglobin, and C-reactive protein (CRP). CONCLUSIONS: Both our results and those in the literature indicate that TTR in geriatric populations is lower than that in the general population. Most patients had an insufficient TTR, exposing them to an increased risk of thromboembolic and hemorrhagic events. These data provide a perspective on poor-quality anticoagulation and illustrates the difficulty of using VKAs in geriatric patients.