Journal of nuclear medicine : official publication, Society of Nuclear Medicine最新文献

Anger SPECT monitoring of [¹⁷⁷Lu]Lu-prostate-specific membrane antigen (PSMA) therapy provides significant prognostic information about patients with metastatic castration-resistant prostate cancer (mCRPC) but with 36- to 90-min recording times and partial body coverage. This study assesses the prognostic information from a comprehensive analysis of tumor changes from the first to the last [¹⁷⁷Lu]Lu-PSMA therapy injections, as provided by whole-body [¹⁷⁷Lu]Lu SPECT recordings from a high-speed 360° cadmium-zinc-telluride (CZT) camera of mCRPC patients. Methods: We included mCRPC patients treated by [¹⁷⁷Lu]Lu-PSMA-617 injections who underwent [⁶⁸Ga]Ga-PSMA-11 PET before treatment, whole-body 360° [¹⁷⁷Lu]Lu CZT SPECT recordings of only 18 min obtained 24 h after each [¹⁷⁷Lu]Lu-PSMA therapy injection, and plasma prostate-specific antigen (PSA) measurements before each injection. We used Cox proportional hazards models to predict overall survival (OS) according to PSA evolution during treatment, as well as tumor SUV_max, SUV_mean, total uptake volume, and total lesion activity (TLA; total uptake volume × SUV_mean) extracted from [⁶⁸Ga]Ga-PSMA-11 PET and the first and last [¹⁷⁷Lu]Lu SPECT scans. Results: We included 72 patients with a median age of 71 y (interquartile range, 64-77 y), treated with up to 6 [¹⁷⁷Lu]Lu-PSMA injections. Among 57 patients with at least 2 [¹⁷⁷Lu]Lu-PSMA treatment cycles, 35 (61%) died during a follow-up of 12.0 mo (range, 4.9-17.5 mo) from the last [¹⁷⁷Lu]Lu-PSMA injection. Most PSA, PET, and SPECT variables were significant univariate predictors of OS. However, only 2 [¹⁷⁷Lu]Lu SPECT variables were selected as multivariate predictors: SPECT detection of new bone lesions during treatment (P < 0.0001) and final SPECT TLA (P = 0.0007). Means of survival times were 19.7 mo (95% CI, 16.6-22.8 mo) in the 19 patients who showed no new bone lesions and final TLA lower than the median of 750 mL·SUV, 14.4 mo (95% CI, 10.9-18.0 mo) in the 19 patients with only 1 of these 2 criteria, and 6.9 mo (95% CI, 4.5-9.6 mo) in the 19 patients with neither criterion. Conclusion: A comprehensive analysis of tumor changes from the first to the last [¹⁷⁷Lu]Lu-PSMA injections, obtained with fast whole-body 360° [¹⁷⁷Lu]Lu CZT SPECT recordings, provides strong prognostic information about mCRPC patients, outperforming conventional OS predictors such as PSA evolution and [⁶⁸Ga]Ga-PSMA-11 PET variables before treatment.

Prostate-specific membrane antigen (PSMA) PET has the potential to monitor the response to taxane-based chemotherapy in patients with prostate cancer and shows promise for predicting outcomes and improving response evaluation. This retrospective study aimed to determine the prognostic value of [⁶⁸Ga]Ga-PSMA-11 PET (PSMA PET)-derived quantitative tumor burden parameters for overall survival (OS). Methods: Databases from 6 institutions were screened for patients with prostate cancer who underwent PSMA PET and whose serum prostate-specific antigen (PSA) measurements were recorded at baseline and after completing taxane-based chemotherapy. Tumor segmentation was performed using artificial intelligence-based software, and PSMA PET whole-body quantitative parameters were obtained, including PSMA-positive tumor volume (PSMA-VOL), SUV_max, and SUV_mean Univariate Cox regression analyses were used to evaluate the association of whole-body quantitative PSMA parameters and PSA levels with OS. The Harrell concordance index (C-index) was used to determine prognostic accuracy. Optimal cutoffs were determined by maximizing the log-rank statistic. Results: In total, 128 patients were included in the study; 62 (48%) had hormone-sensitive prostate cancer, and 66 (52%) had castration-resistant prostate cancer. At baseline, PSMA-VOL had the highest prognostic value for OS compared with serum PSA, SUV_max, and SUV_mean (C-index of 0.88, 0.80, 0.69, and 0.29, respectively), whereas the percentage change in PSA levels had the highest prognostic value during treatment compared with percentage change in PSMA-VOL, SUV_max, and SUV_mean (C-index of 0.94, 0.85, 0.90, and 0.85, respectively). Conclusion: Baseline and posttherapeutic PSMA PET quantitative parameters are prognostic for OS after taxane-based chemotherapy in patients with metastatic prostate cancer. Baseline PSMA-VOL had the highest prognostic value for OS, whereas changes in PSA levels outperformed changes in quantitative PSMA PET parameters during treatment.

Partial-volume effects (PVEs) arise from the limited spatial resolution of PET and SPECT imaging systems, causing the systematic underestimation of activity concentration in structures that may hold critical diagnostic, treatment, or dosimetric information that impacts patient management. Recovery coefficient (RC)-based partial-volume correction (PVC) is one of the simpler approaches used to correct for partial-volume losses impacting image-based activity estimates in quantitative nuclear medicine. Despite its routine application, RC PVC lacks standardization, underscoring the need for a validated and vetted tool to facilitate consistent use across the community. As part of the MIRDsoft community dosimetry tools project, we have developed MIRDpvc-a worksheet that facilitates a resolution-based RC PVC approach that enables shape-specific corrections, alongside conventional RC curve corrections. In this work, we describe the MIRDpvc software and validate the new PVC methodology using various simulated studies. The recovery coefficient equivalent resolution-geometric mean (RECOVER-GM) model implemented in MIRDpvc represents a straightforward and effective improvement in the quantitative accuracy of mean activity concentrations within volumes of interest in PET and SPECT images, accounting for both spill-out and spill-in PVEs and incorporating shape-specific corrections. The simplicity and accessibility of the software make it practical for clinical implementation, providing a significant improvement over methods that rely on spherical assumptions. The RECOVER-GM method incorporates lesion geometry while maintaining computational efficiency, highlighting its practical advantages for PVC in PET and SPECT imaging.

A significant number of patients report persistent fatigue and difficulty concentrating after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a condition known as post-coronavirus disease 2019 (post-COVID) syndrome. The underlying mechanisms for these complaints remain poorly understood. Dysregulated immune and neurologic systems may play a role in the pathophysiology of post-COVID syndrome. A target providing direct information on immune activation is the 18-kDa translocator protein (TSPO), which is upregulated in activated microglia. The PET tracer N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)5,7dimethylpyrazolo[1,5a]pyrimidin-3-yl)acetamide ([¹⁸F]DPA-714) binds with high affinity to TSPO and serves as a biomarker for neuroinflammation. We aimed to assess whole-body inflammatory activity with TSPO PET in individuals with and without persistent severe fatigue and difficulty concentrating 2 y after infection with SARS-CoV-2 as well as its association with complaint severity. Methods: In this cross-sectional cohort study, we evaluated 47 post-COVID individuals, 33 of whom had severe fatigue and difficulty concentrating (age, 50 ± 8 y; 27 ± 9 mo after initial infection) and 14 who did not have these complaints (age, 47 ± 9 y; 25 ± 10 mo after initial infection). All individuals were high-affinity binders according to their TSPO genotype and completed whole-body 60-min dynamic [¹⁸F]DPA-714 PET with arterial sampling, MRI, genotyping, and questionnaires. Tracer binding was quantified using binding potential for cerebral regions and inhibitory constant or total distribution volume for extracerebral regions. Parameters were compared between 33 individuals with persistent complaints (severe fatigue and difficulty concentrating) and 14 without, and associations between parameters were assessed. Results: We found globally increased cerebral [¹⁸F]DPA-714 binding in some individuals reporting persistent complaints when compared with individuals without these complaints. No group-level differences were found in extracerebral binding. Large variability in cerebral and extracerebral binding was observed among individuals. Cerebral and extracerebral binding levels were not correlated with each other or with complaint severity. Conclusion: Increased specific [¹⁸F]DPA-714 binding was found in some individuals with post-COVID syndrome, indicating the presence of an inflammatory subtype and further supporting the role of neuroinflammation in subtypes of post-COVID syndrome.

Patient outcomes in metabolic dysfunction-associated steatohepatitis (MASH) are associated with the presence and stage of liver fibrosis. Activated hepatic stellate cells are a key mediator of MASH fibrogenesis and show increased expression of integrin α_vβ₃, making it a promising target for imaging and treatment of liver fibrosis. The ability to noninvasively measure target engagement of integrin inhibitors is key to understanding their chances of success in clinical development. Methods: Target engagement was assessed using PET imaging of an arginine-glycine-aspartic acid (RGD)-based integrin-binding tracer ¹⁸F-FPP-RGD₂ Mice were fed a choline-deficient, ʟ-amino acid-defined, high-fat diet (CDAHFD) or control diet for 2, 6, 10, or 14 wk to induce fibrosis (n = 6/time point). PET was conducted on subsequent days without and with an oral dose of integrin α_vβ₃ antagonist IDL-2965 (10 mg/kg). The antifibrotic activity was evaluated in mice fed CDAHFD for 12 wk and treated with daily oral IDL-2965 (10 mg/kg) or vehicle in weeks 5-12. Integrin β₃ expression was evaluated in liver biopsies from patients with varying degrees of fibrosis. Results: Significantly higher liver uptake of the integrin-binding PET tracer was found in MASH mice than in age-matched controls and increased with the duration of CDAHFD up to 10 wk. At each stage of fibrotic progression, a single oral dose of IDL-2965 significantly reduced hepatic ¹⁸F-FPP-RGD₂ uptake, consistent with strong IDL-2965 target engagement. In a separate study, therapeutic administration of IDL-2965 significantly reduced multiple measures of CDAHFD-induced liver fibrosis, including histologic fibrosis scores, Sirius Red-stained area, hydroxyproline content, Col1α1 messenger RNA expression, and plasma cytokeratin-18. In human liver biopsies, integrin β₃ expression increased with increasing fibrosis score. Conclusion: Increased expression of integrin α_vβ₃ and strong target engagement by IDL-2965 in the CDAHFD-induced MASH model can be detected in vivo using the integrin-binding PET tracer ¹⁸F-FPP-RGD₂ Consistent with strong target engagement, therapeutic administration of IDL-2965 significantly reduced multiple measures of CDAHFD-induced hepatic fibrosis.