Pretherapeutic PSMA PET-Derived Semiquantitative Parameters as Predictors of PSA Response in Patients with mCRPC Receiving [ 177 Lu]Lu-PSMA-617 Radioligand Therapy.

Objective [ 177 Lu]Lu-prostate-specific membrane antigen (PSMA)-617 radioligand therapy (RLT) shows promise for metastatic castration-resistant prostate cancer (mCRPC) patients with positive PSMA positron emission tomography (PET) imaging. Identifying high-risk patients is crucial. We evaluated pretherapeutic PSMA PET-derived parameters to predict prostate-specific antigen (PSA) response in patients undergoing [ 177 Lu]Lu-PSMA-617 RLT. Materials and Methods We conducted a retrospective analysis among 27 patients (mean age: 71.0 ± 9.5 years; range: 52-85 years) who underwent PSMA PET/computed tomography (CT) and subsequent [ 177 Lu]Lu-PSMA-617 RLT between March 2019 and January 2023. After excluding patients with liver metastases, the number of patients left for analysis was 21 (14 responders and 7 nonresponders). Tumors were semiautomatically delineated with calculation of total tumor volume (PSMA-TV), lesion uptake (PSMA-TLU = PSMA-TV * standardized uptake value [SUV]mean), and lesion quotient (PSMA-TLQ = PSMA-TV/SUVmean) for each patient. Semiquantitative parameters were analyzed only in patients with mCRPC and no liver metastasis. Results In total, 17/27 patients (62.96%) had a decline in PSA levels; 15/27 patients (55.56%) experienced a decline of > 50%. Pretherapeutic PSMA PET/CT results revealed significant differences in PSMA-TV ( p = 0.003), PSMA-TLU ( p = 0.013), and PSMA-TLQ ( p = 0.011) between responders and nonresponders. SUVmax was significantly correlated to the best percentage change in PSA response after 177 Lu-PSMA-617 treatment ( r = -0.79, p = 0.006). No association was observed between PSMA-TV ( p = 0.367), PSMA-TLU ( p = 0.128), and PSMA-TLQ ( p = 0.556), with the best percentage change in PSA response after 177 Lu-PSMA-617 therapy. Conclusion Pretherapeutic PSMA PET-derived PSMA-TV, PSMA-TLU, and PSMA-TLQ were significant negative predictors of PSA response in patients with mCRPC and no liver metastasis receiving [ 177 Lu]Lu-PSMA-617 RLT.

How to design a theranostic trial?

The field of nuclear theranostic clinical trials is continuously expanding as an increasing number of novel agents and treatment combinations are explored for treating advanced and metastatic cancers. Moving from 'bench-to-bedside' is oftentimes a complex and lengthy process. The objective of this overview is to explore the basic elements involved in designing clinical trials with a special focus on theranostics in nuclear medicine. The 'bench-to-bedside' journey involves translating basic scientific research into patient-effective treatments. Preclinical studies, a crucial initial step, are a complex process encompassing in vitro experiments, in vivo studies, and animal models to explore hypotheses in humans. Clinical trials follow, with predefined phases assessing safety, effectiveness, and comparisons to existing treatments. This process demands investments in data management, statistics, good clinical practice (GCP) accreditations, and collaborative efforts for funding and sustainable pricing. Theranostics, merging diagnostics and personalized treatment, is at the forefront. Continuous efforts to enhance existing agents involve reducing adverse effects, exploring new indications, and incorporating advanced imaging modalities. Radionuclide therapy, unique with non-uniform distribution and complex radiobiology, plays a distinct role. This article explores trends and challenges in each clinical trial phase in light of the emerging field of theranostics in nuclear medicine, emphasizing meticulous trial design, dosimetry optimization, and the necessity of collaborative stakeholder efforts for successful implementation.

Head-to-head comparison of 18F-FDG and 18F-FES PET/CT for initial staging of ER-positive breast cancer patients.

PURPOSE: To compare the diagnostic performance of 18F-fluorodeoxyglucose (18F-FDG) and 18F-fluoroestradiol (18F-FES) positron emission tomography/computed tomography (PET/CT) for initial staging of estrogen receptor (ER) positive breast cancer. METHODS: Twenty-eight patients with ER-positive breast cancer underwent 18F-FDG and 18F-FES PET/CT for initial staging. Diagnostic performance and concordance rates were analyzed for both radiotracers. Semiquantitative parameters of maximum standardized uptake value (SUVmax) and tumor-to-normal ratio (T/N ratio) were compared using Wilcoxon signed-rank test. Factors potentially affecting the degree of radiotracer uptake were analyzed by multi-level linear regression analysis. RESULTS: The overall diagnostic performance of 18F-FES was comparable to 18F-FDG, except for higher specificity and NPV, with sensitivity, specificity, PPV, NPV, and accuracy of 87.56%, 100%, 100%, 35.14%, and 88.35%, respectively, for 18F-FES and 83.94%, 30.77%, 94.74%, 11.43%, and 95.37%, respectively, for 18F-FDG. Diagnostic performance of strong ER expression was better in 18F-FES but worse for 18F-FDG. There was a correlation of mucinous cell type and Allred score 7-8 with 18F-FES uptake, with correlation coefficients of 26.65 (19.28, 34.02), 5.90 (- 0.005, 11.81), and p-value of < 0.001, 0.05, respectively. Meanwhile, luminal B and Ki-67 were related to 18F-FDG uptake, with correlation coefficients of 2.76 (1.10, 0.20), 0.11 (0.01, 0.2), and p-value of 0.018, 0.025, respectively. CONCLUSION: Diagnostic performance of 18F-FES is comparable to 18F-FDG, but better for strongly ER-positive breast cancer. Combination of 18F-FES and 18F-FDG would potentially overcome the limitations of each tracer with more accurate staging.

Assessing the variability and correlation between SUV and ADC parameters of head and neck cancers derived from simultaneous PET/MRI: A single-center study.

OBJECTIVE: Intratumoral heterogeneity is associated with poor outcomes in head and neck cancer (HNC) patients owing to chemoradiotherapy resistance. [18 F]-FDG positron emission tomography (PET) / Magnetic Resonance Imaging (MRI) provides spatial information about tumor mass, allowing intratumor heterogeneity assessment through histogram analysis. However, variability in quantitative PET/MRI parameter measurements could influence their reliability in assessing patient prognosis. Therefore, to use standardized uptake value (SUV) and apparent diffusion coefficient (ADC) parameters for assessing tumor response, this study aimed to measure SUV and ADC's variability and assess their relationship in HNC. METHODS: First, ADC variability was measured in an in-house diffusion phantom and in five healthy volunteers. The SUV variability was only measured with the NEMA phantom using a clinical imaging protocol. Furthermore, simultaneous PET/MRI data of 11 HNC patients were retrospectively collected from the National Cyclotron and PET center in Chulabhorn Hospital. Tumor contours were manually drawn from PET images by an experienced nuclear medicine radiologist before tumor volume segmentation. Next, SUV and ADC's histogram were used to extract statistic variables of ADC and SUV: mean, median, min, max, skewness, kurtosis, and 5th , 10th , 25th , 50th , 75th , 90th , and 95th percentiles. Finally, the correlation between the statistic variables of ADC and SUV, as well as Metabolic Tumor volume and Total Lesion Glycolysis parameters was assessed using Pearson's correlation. RESULTS: This pilot study showed that both parameters' maximum coefficient of variation was 13.9% and 9.8% in the phantom and in vivo, respectively. Furthermore, we found a strong and negative correlation between SUVmax and ADVmed (r = -0.75, P = 0.01). CONCLUSION: The SUV and ADC obtained by simultaneous PET/MRI can be potentially used as an imaging biomarker for assessing intratumoral heterogeneity in patients with HNC. The low variability and relationship between SUV and ADC could allow multimodal prediction of tumor response in future studies.

Comparison of performance between an F 18 -FDG PET normal brain template and a commercial template using the MIMneuro software.

Purpose: The aim of this study was to create and validate a normal brain template of F 18 -fluorodeoxyglucose ( F 18 - FDG ) uptake using the MIMneuro software to improve clinical practice. Approach: One hundred and nine volunteers underwent an F 18 - FDG positron emission tomography/computed tomography scan. Sixty-three participants with normal Alzheimer's disease (AD) biomarkers were used to create a template. A group of 23 participants with abnormal AD biomarkers and an additional group of 23 participants with normal AD biomarkers were used to validate the performance of the generated template. The MIMneuro software was used for the analysis and template creation. The performance of our newly created template was compared with that of the MIMneuro software template in the validation groups. Results were confirmed by visual analysis by nuclear medicine physicians. Results: Our created template provided higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV; 90%, 97.83%, 100%, and 100%, respectively) than did the MIMneuro template when using the positive validation group. Similarly, slightly higher performance was observed for our template than for the MIMneuro template in the negative validation group (the highest specificity and NPV were 100% and 100%, respectively). Conclusions: Our normal brain template for F 18 - FDG was shown to be clinically useful because it enabled more accurate discrimination between aging brain and patients with AD. Thus, the template may improve the accuracy of AD diagnoses.

Comparisons of Quantitative Parameters of Ga-68-Labelled Fibroblast Activating Protein Inhibitor (FAPI) PET/CT and [18F]F-FDG PET/CT in Patients with Liver Malignancies.

PURPOSE: To compare quantitative parameters and tumour detection rates of [68 Ga]Ga-FAPI PET/CT with those of dedicated liver PET/MRI and 18F-FDG PET in patients with liver malignancies. PROCEDURES: Twenty-seven patients (29 imaging studies) with diagnosed or suspected liver malignancies who underwent [68 Ga]Ga-FAPI-46 PET/CT, liver PET/MRI, and [18F]FDG PET/CT between September 2020 and June 2021 were retrospectively analysed. MRI findings were used as the reference standard for diagnosis. RESULTS: The 27 patients had a median age of 68 years (interquartile range: 60-74 years; 21 men). Primary intrahepatic tumours were reported in 13 patients (15 imaging studies) with cholangiocarcinoma (CCA) and in 14 patients with hepatocellular carcinoma (HCC). All intrahepatic lesions detectable on MRI were also detected on [68 Ga]Ga-FAPI-46 PET/CT giving a sensitivity of 100% (19/19), whereas the sensitivity of [18F]FDG PET/CT was 58% (11/19). All intrahepatic lesions were detected on [68 Ga]Ga-FAPI-46 PET/CT, on which they showed higher activity (median SUVmax: 15.61 vs. 5.17; P < .001) and higher target-to-background ratio (TBR; median, 15.90 vs. 1.69, P < .001) than on [18F]FDG, especially in patients with CCA (median TBR, 21.08 vs. 1.47, respectively; P < .001). The uptake positivity rate in regional node metastasis was 100% (12/12) on [68 Ga]Ga-FAPI-46 PET/CT compared with 58% (7/12) on [18F]FDG PET/CT. All patients with distant metastasis (100%, 14/14) were detected on both [18F]FDG and [68 Ga]Ga-FAPI-46 PET/CT imaging, although more distant metastatic lesions were detected on [68 Ga]Ga-FAPI-46 PET/CT than on [18F]FDG (96% (42/44) vs. 89% (39/44), respectively). CONCLUSION: [68 Ga]Ga-FAPI PET/CT with dedicated liver PET/MRI shows potential for superior detection of hepatic malignancy compared with [18F]FDG PET/CT or MRI alone.

Alterations in 18F-FDG PET/MRI and 15O-Water PET Brain Findings in Patients With Neurological Symptoms After COVID-19 Vaccination: A Pilot Study.

PURPOSE: This study aimed to investigate functional abnormalities in the brain of patients with neurological adverse effects following COVID-19 (coronavirus disease 2019) vaccination using 18F-FDG PET/MRI and 15O-water PET. METHODS: Eight patients (1 man and 7 women, aged 26-47 years [median age, 36.5 years]) who experienced neurological symptoms after the first COVID-19 vaccination underwent CT, MRI, 18F-FDG PET/MRI, and 15O-water PET of the brain. After 7 days, each patient underwent a follow-up 18F-FDG PET/MRI and 15O-water PET of the brain. Imaging data were analyzed using visual and semiquantitative analyses, which included a cluster subtraction workflow (P = 0.05). RESULTS: There was no evidence of vascular abnormalities, acute infarction, or hemorrhage on the CT or MRI scans. On the 15O-water PET images, 1 patient had mildly significant decreases in perfusion in the bilateral thalamus and bilateral cerebellum, and another patient showed a diffuse increase in perfusion in the cerebral white matter. The visual and semiquantitative analyses showed hypometabolism in the bilateral parietal lobes in all 8 patients on both the first and follow-up 18F-FDG PET/MRI scans. Metabolic changes in the bilateral cuneus were also observed during the first visit; all patients exhibited neurological symptoms. Moreover, 6 patients showed hypometabolism, and 2 patients showed hypermetabolism. CONCLUSION: All regions of metabolic abnormality were part of the fear network model that has been implicated in anxiety. Our study findings support the concepts of and provide evidence for the immunization stress-related response and the biopsychosocial model.

Intense 68Ga-FAPI-46 Activity in Lesions of Recurrent Ovarian Clear Cell Carcinoma That Were Negative on FDG PET/CT Study.

ABSTRACT: A 55-year-old woman with recurrent ovarian clear cell carcinoma who underwent complete surgical staging and completed chemotherapy session approximately 7 months before. She presented with increased CA-125 levels. 68Ga-FAPI-46 PET showed significantly higher tumor-to-background contrast of recurrent intra-abdominal node metastases and distant metastases, which were undetectable in the 18F-FDG PET. These findings changed the patient management. Larger studies with comparisons with other imaging modalities are required to validate the diagnostic performance.

Abnormality Pattern of F-18 FDG PET Whole Body with Functional MRI Brain in Post-Acute COVID-19.

Purpose: The study aimed to investigate imaging abnormalities associated with post-acute COVID-19 using F-18 FDG PET/CT and PET/ rsfMRI brain. Methods: We retrospectively recruited 13 patients with post-acute COVID-19. The post-acute COVID-19 symptoms and neuropsychiatric tests were performed before F-18 FDG PET/CT whole body with PET/rsfMRI brain. Qualitative and semiquantitative analyses were also conducted in both whole body and brain images. Results: Among the 13 patients, 8 (61.5%) had myositis, followed by 8 (61.5%) with vasculitis (mainly in the thoracic aorta), and 7 (53.8%) with lung abnormalities.. Interestingly, one patient with a very high serum RBD IgG antibody demonstrated diffuse myositis throughout the body which potentially associated with immune-mediated myositis. One patient experienced psoriasis exacerbation with autoimmune-mediated after COVID-19. Most patients had multiple areas of abnormal brain connectivity involving the frontal and parieto-temporo-occipital lobes, as well as the thalamus. Conclusion: The whole body F-18 FDG PET can be a potential tool to assess inflammatory process and support the hyperinflammatory etiology, mainly for lesions in skeletal muscle, vascular wall, and lung, as well as, multiple brain abnormalities in post-acute COVID-19. Nonetheless, further studies are recommended to confirm the results.

Head-to-Head Comparison of 68Ga-FAPI-46 and 18F-FDG PET/CT for Evaluation of Head and Neck Squamous Cell Carcinoma: A Single-Center Exploratory Study.

68Ga-conjugated fibroblast activation protein inhibitor (68Ga-FAPI) has become an attractive agent for PET. This study aimed to compare 68Ga-FAPI-46 PET/CT with 18F-FDG PET/CT for detecting primary cancer and metastatic lesions in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Twelve patients and 28 patients with HNSCC underwent 68Ga-FAPI-46 and 18F-FDG PET/CT for initial staging and recurrence detection, respectively. The concordance and diagnostic accuracy of both tracers were analyzed. Semiquantitative parameters, including SUVmax, SUVmean, and tumor-to-background ratio, were compared. Fibroblast activation protein (FAP) expression tumor volume and total lesion FAP expression of 68Ga-FAPI-46 were compared with metabolic tumor volume and total lesion glycolysis of 18F-FDG, respectively. Differences between semiquantitative parameters were analyzed using paired t testing. Results:68Ga-FAPI-46 PET/CT was 83.3% and 96.4% concordant with 18F-FDG PET/CT for initial staging and recurrence detection, respectively. Eighteen lesions had histopathologic validation, and both tracers displayed 100% sensitivity, 50% specificity, and 94.4% accuracy for lesion-based analysis. FAP expression tumor volume was greater than metabolic tumor volume (P < 0.05), but no significant differences were observed for the other parameters. Conclusion:68Ga-FAPI-46 PET/CT showed good concordance with, and comparable diagnostic performance to, 18F-FDG PET/CT for initial staging and recurrence detection in HNSCC patients.

Clinical impact of quantitative [15O] H2O PET/CT myocardial perfusion imaging on decision-making regarding invasive management of coronary artery disease.

BACKGROUND: This study was performed to determine the impact of oxygen-15-labeled water ([15O] H2O) positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging (MPI) on referral for invasive coronary angiography (ICA) and revascularization. METHODS: This study involved 57 patients who underwent [15O] H2O PET/CT MPI for evaluation of coronary artery disease (CAD). Data of referral for ICA and revascularization, clinical symptoms, and cardiac events within 6 months after MPI were assessed. Logistic regression was used to determine the predictors for referral and revascularization. The diagnostic values of hyperemic myocardial blood flow (MBF) and coronary flow reserve (CFR) were calculated. RESULTS: Normal and abnormal MPI findings were observed in 18 (32%) and 39 (68%) patients, respectively. The referral rate was significantly different between the normal and abnormal MPI groups (5.6% and 48.7%, respectively; P = .002). Revascularization rate of abnormal MPI group was 40.0%. There were significant differences of hyperemic MBF and CFR between patients with and without referral. Hyperemic MBF was significant predictor for referral (OR 15.24, 95% CI 3.39-68.55, P < .005) and revascularization (OR 28.57, 95% CI 3.08-265.33, P < .005). CONCLUSION: [15O] H2O PET/CT MPI showed a clinical impact on decision-making regarding invasive procedure for management of CAD.

68Ga-FAPI-46 PET/MR Detects Recurrent Cholangiocarcinoma and Intraductal Papillary Mucinous Neoplasm in a Patient Showing Increasing CEA with Negative 18F-FDG PET/CT and Conventional CT.

A patient with intrahepatic cholangiocarcinoma who underwent hepatic resection with completed neoadjuvant chemotherapy presented with increased CEA levels. Previous whole abdominal and chest CT scan revealed no evidence of local recurrence or metastasis. 68 Ga-FAPI-46 PET showed significantly higher tumor-to-background contrast of recurrent tumor and nodal metastasis, which were undetectable in the FDG PET or conventional CT scan. These findings changed patient management. Larger studies with histopathological correlation and comparisons with other imaging modalities are required to validate the diagnostic performance. Moreover, a cystic lesion with FAPI uptake at the neck to the proximal body of the pancreas without FDG uptake is also incidentally noted. Differential diagnoses include sided branch IPMN and serous cystadenoma.