Kaan Akçay

Purpose To develop and validate the Istanbul [⁶⁸Ga]Ga-PSMA PET/CT Criteria (IPPC), a standardized imaging framework designed to identify clinically significant prostate cancer (csPCa) and improve selection of candidates for active surveillance (AS). Methods [⁶⁸Ga]Ga-PSMA PET/CT scans and histopathology from 163 men with biopsy-proven International Society of Urological Pathology (ISUP) Grade Group (GG) 1–2 prostate cancer who underwent radical prostatectomy were retrospectively reviewed by a multidisciplinary panel of nuclear medicine physicians, radiologists, and urologists. Imaging characteristics—including uptake pattern, morphology, localization, and SUVmax—were iteratively analyzed to define three categories: IPPC-1 (indolent), IPPC-2 (indeterminate), and IPPC-3 (csPCa-suspected). Delayed pelvic acquisitions were used as the primary dataset to enhance lesion definition and interpretability. Reproducibility was evaluated in 56 GG1 patients using Cohen’s and Fleiss’ κ statistics. Correlations between PSA, SUVmax, and IPPC categories were assessed, and ROC curve analysis was performed to determine the optimal SUVmax threshold for csPCa detection. Results Pathological upgrading occurred in 40% of all cases (74% GG1, 20% GG2). Among 56 GG1 patients, upgrading was 76%. SUVmax and PSA were significantly higher in IPPC-3 than in IPPC-2 (SUVmax 16.3 vs. 6.5, p < 0.001; PSA 7.8 vs. 5.3 ng/mL, p < 0.05). ROC analysis yielded an AUC = 0.76 with an optimal SUVmax cut-off of 8.21 (sensitivity 55%, specificity 90%). All lesions with SUVmax ≥ 12.0 corresponded to csPCa. Interobserver agreement was substantial (κ ≈ 0.70–0.74) and intraobserver concordance strong (κ ≈ 0.80–0.90), confirming high reproducibility. Conclusion IPPC provides a reproducible, biologically grounded method that integrates SUVmax, morphology, and anatomical localization to non-invasively refine AS eligibility. By identifying patients at genuine risk for csPCa while minimizing unnecessary biopsies, IPPC may improve confidence and adherence in AS management. Prospective multicentre validation within the ongoing I-SELECT trial (NCT07168616) will determine its broader clinical applicability.

This study aimed to investigate the potential efficacy of [⁶⁸Ga]Ga-FAP-2286 PET/CT in evaluating treatment response in patients with gastrointestinal system malignancies. Patients with histopathologically confirmed gastrointestinal malignancies who underwent [⁶⁸Ga]Ga-FAP-2286 PET/CT for treatment response assessment between November 2020 and January 2025 were included. All images were evaluated by three experienced nuclear medicine physicians. The maximum standardized uptake values (SUVmax), total tumor volumes, and total lesion FAP expression values of primary tumors and metastases were recorded. At the same time, serum tumor marker levels were analyzed. Imaging responses were assessed separately according to PERCIST criteria on [⁶⁸Ga]Ga-FAP-2286 PET/CT and RECIST criteria on CT. Survival outcomes were analyzed using the Kaplan-Meier method, and their association with treatment response on [⁶⁸Ga]Ga-FAP-2286 PET/CT was assessed using the Log-Rank (Mantel-Cox) test and Cox proportional hazards regression. A p-value < 0.05 was considered statistically significant in all analyses. A total of 100 [⁶⁸Ga]Ga-FAP-2286 PET/CT scans were performed in 50 patients (mean age: 61.62 ± 12.95), both before and after treatment. Among the included patients, 70% had gastric cancer, 14% had colon cancer, 8% had pancreatic cancer, 4% had appendiceal cancer, 2% had hepatocellular carcinoma (HCC), and 2% had cholangiocellular carcinoma. Primary/recurrent tumor lesions were observed in 62% of patients, lymph node metastases in 24%, visceral metastases in 10%, peritoneal metastases in 76%, and bone metastases in 14%. A strong correlation was found between tumor volumes and total lesion FAP expression measured by [⁶⁸Ga]Ga-FAP-2286 PET/CT and the corresponding serum tumor markers (Area Under the Curve [AUC] for delta tumor volume and total lesion FAP expression = 0.875). There was a statistically significant and near-perfect concordance between [⁶⁸Ga]Ga-FAP-2286 PET PERCIST and CT RECIST criteria (Kappa = 0.833, p < 0.05). Moderate agreement was found for primary tumors (Kappa = 0.526, p < 0.05) and bone metastases (Kappa = 0.657, p < 0.05), while excellent agreement was observed for lymph node (Kappa = 1.0, p < 0.05), peritoneal (Kappa = 0.815, p < 0.05), and visceral metastases (Kappa = 1.0, p < 0.05). According to the Kaplan-Meier analysis, treatment response assessed by [⁶⁸Ga]Ga-FAP-2286 PET/CT was predictive of overall survival (p = 0.02). Median overall survival was 7.6 months in patients with progressive disease and 19.8 months in those with stable disease, as defined by PERCIST criteria. Median survival was not reached in patients showing partial or complete response. In gastrointestinal system malignancies, a strong correlation was observed between serum tumor markers and both total tumor volumes and total lesion FAP expression values derived from [⁶⁸Ga]Ga-FAP-2286 PET imaging. Additionally, molecular response assessed by [⁶⁸Ga]Ga-FAP-2286 PET/CT was predictive of overall survival. [⁶⁸Ga]Ga-FAP-2286 PET/CT appears to be an effective tool for assessing treatment response and monitoring patients with gastrointestinal malignancies.

Cancer Integrin Imaging with [68Ga]Ga-Trivehexin PET/CT for a Patient with Breast Cancer and Neuroendocrine Neoplasm: A Case of Both (18F)FDG PET/CT and [68Ga]Ga-DOTATATE Positive but Integrin avβ6 Negative Lesion on [68Ga]Ga-Trivehexin PET - Molecular Imaging and Radionuclide Therapy

Impact of 68Ga-FAPi PET/CT on Staging or Restaging Digestive System Tumors in Patients with Negative or Equivocal 18F-FDG PET/CT Findings - Molecular Imaging and Radionuclide Therapy

Improved Accuracy and Reliability of PRIMARY Scoring Using Delayed [68Ga] Ga-PSMA PET/CT Imaging - Molecular Imaging and Radionuclide Therapy

Background: The combination of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) with androgen receptor pathway inhibitors (ARPIs) has shown promise in metastatic castration-resistant prostate cancer (mCRPC). However, real-world data on the efficacy and safety of this combination are limited. This study aimed to evaluate the impact of combination therapy with Lu-177 PSMA-617 RLT and ARPIs on progression-free survival (PFS) and overall survival (OS) in patients with mCRPC. Methods: In this retrospective study, 104 mCRPC patients receiving Lu-177 PSMA-617 RLT at our institution between December 2017 and January 2024 were divided into the following two groups those receiving Lu-177 PSMA-617 RLT plus ARPI (n = 34) and those receiving Lu-177 PSMA-617 RLT alone (n = 70). Patients received 150 to 200 millicuries Lu-177 PSMA-617 RLT in each cycle. PFS and zOS were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Results: The combination therapy significantly prolonged median PFS compared to Lu-177 PSMA-617 RLT alone (11 vs. 5.6 months; HR, 0.47; 95% CI, 0.28–0.79; p < 0.01). A trend towards improved OS was also observed in the combination group (20.3 vs. 15.9 months; HR, 0.58; 95% CI, 0.33–1.02; p = 0.06). Age was a significant predictor of OS (21.2 vs. 12.4 months for younger vs. older patients; p < 0.01), while Gleason score and visceral involvement did not significantly impact PFS. The safety profile indicated that adverse effects were generally comparable between the two groups, with no statistically significant differences in the incidence of anemia, neutropenia, thrombocytopenia, nephrotoxicity, or hepatotoxicity. Conclusions: This study provides evidence that combining Lu-177 PSMA-617 RLT with ARPIs may significantly improve PFS in mCRPC patients. The potential OS benefit warrants further investigation in larger prospective trials. Age should be considered when making treatment decisions for mCRPC patients.

Neuroendocrine tumors (NETs) of the breast represent 1% of breast carcinomas. Histopathological misinterpretation of breast NET is common. We present the case of a female patient who had a breast mass diagnosed as invasive ductal carcinoma initially by histopathological examination. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) revealed 2 ametabolic hypodense liver lesions. Subsequently, the patient underwent fibroblast activation protein inhibitor (FAPI)-PET/CT, which did not reveal any FAP expression in the liver lesions, but increased FAP expression was observed in the soft tissue mass of the mesenteric root. Consequently, the pathology of the biopsy taken from the nodule in the right breast was revised, and a diagnosis of grade 2 NET was established. The benefit of FAPI-PET/CT on NETs has been previously investigated. Further prospective studies are required to establish the role of FAPI-PET/CT in NET management.

Purpose In our study, our aim was to investigate the role of [⁶⁸ Ga]Ga-PSMA-11 PET /CT imaging in the diagnosis of clinically significant prostate cancer (csPCa) (ISUP GG 2 and higher) in patients initially diagnosed with ISUP GG 1 and 2 after prostate biopsy. Materials and methods We retrospectively reviewed 147 patient records in whom [⁶⁸ Ga]Ga-PSMA-11 PET/CT imaging was performed preoperatively. All patients were initially diagnosed with ISUP GG 1 and 2 PCa by biopsy. Final pathology reports were obtained after radical prostatectomy. The [⁶⁸ Ga]Ga-PSMA-11 PET/CT images were evaluated to determine the PRIMARY score. Patients’ mpMRI-PIRADS scores were also recorded when available and analyzed in correlation with the pathology results. Results For the 114 patients scored using PRIMARY, 19 out of 37 patients with scores of 1 and 2 (51%) were diagnosed with csPCa. Of the 77 patients with PRIMARY scores between 3 and 5, 64 (83%) had csPCa. Notably, every patient with a PRIMARY score of 5 had csPCa. PRIMARY scoring had a sensitivity of 77% and specificity of 58%, with a positive predictive value of 83%. A moderate correlation was observed between PRIMARY scores and ISUP GG (Rho = 0.54, p < 0.001). In contrast, the PIRADS score displayed a sensitivity and specificity of 86% and 25% respectively, with a positive predictive value of 68%. No substantial correlation was found between PIRADS and ISUP GG. Statistical analysis revealed a significant correlation between PRIMARY and ISUP GG (p < 0.001), but not between PIRADS and ISUP GG (p = 0.281). Comparatively, PRIMARY scoring was significantly more reliable than PIRADS scoring in identifying csPCa. Conclusion [⁶⁸ Ga]Ga-PSMA-11 PET/CT imaging is promising for distinguishing high-risk prostate cancer patients from those apt for active surveillance, potentially aiding in the identification of csPCa.

This study aimed to evaluate the stability, safety, and efficacy of alpha-targeted therapy with [²²⁵Ac]Ac-DOTATATE in patients with grade 1/2 metastatic neuroendocrine tumors (NETs). This retrospective cohort included patients (n=11) with metastatic NETs from different primary sites (bronchial, pancreatic, nonpancreatic gastroenteropancreatic NETs, paraganglioma, and unknown primary site) treated with [²²⁵Ac]Ac-DOTATATE with a mean activity of 8.2±0.6 MBq (range: 7.5-10.0 MBq) at our institution between November 2019 and March 2022. The in vivo and in vitro stability of [²²⁵Ac]Ac-DOTATATE was calculated. The safety profile was evaluated according to the CTCAE-v5.0. Treatment efficacy was evaluated according to [⁶⁸Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) images and the RECIST 1.1 criteria. Patients had 73% (n=8) lymph node metastases, 91% (n=10) liver metastases, 36% (n=4) lung metastases, and 73% (n=8) bone metastases. All but one patient was refractory to treatment with [¹⁷⁷Lu]Lu-DOTATATE. [²²⁵Ac]Ac-DOTATATE was stable for at least 5 h in vitro (in saline) and 3 h in vivo (urine and blood samples). Grade 2 renal toxicity and grade 2 hematotoxicity were observed in one patient. No grade 3-4 toxicities were reported. According to post-treatment [⁶⁸Ga]Ga-DOTATATE PET/CT (n=9), 11% (n=1) had progressive disease, 44.4% (n=4) had stable disease, and 44.4% (n=4) had a partial response. The disease control rate was 89% (n=8). The median progression-free survival estimated according to Kaplan-Meier analysis was 12 months. The preliminary results of this study suggest that [²²⁵Ac]Ac-DOTATATE is stable, safe, and effective for treating advanced and [¹⁷⁷Lu] Lu-DOTATATE-refractory NETs. However, prospective studies are needed to determine the impact of treatment on overall survival and to uncover potential side effects.