Foregut and hindgut neuroendocrine tumors (NETs) contribute significantly to the global NET burden especially in Asian population; however, these cohorts are sparse and underrepresented in current trials assessing peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic (GEP) NETs. This single-centre study evaluates the efficacy and safety of PRRT in advanced foregut and hindgut NETs. Retrospective data evaluation of consecutive patients with biopsy-proven metastatic foregut (gastric, lung and thymic NETs) and hindgut NETs (colorectal, anal and sacral NETs) who underwent PRRT from 2014 to 2024 at a tertiary care hospital was done. Up to four cycles of 177Lu-DOTATATE (7.4 GBq/cycle) were administered intravenously every 6–8 weeks along with nephroprotection. Interim and end-of-treatment 68Ga-DOTANOC PET/CT scans were acquired for response evaluation, based on RECIST v1.1. Objective response rate (ORR), disease control rate (DCR), best biochemical response, toxicity profile, quality-of-life scores, progression-free survival (PFS) and overall survival (OS) were assessed. Thirty-four patients (median age-56 yrs) with foregut (n = 16) and hindgut (n = 18) NETs received a total of 111 cycles (range 1–4) of 177Lu-DOTATATE (median cumulative activity 26.5 GBq). The best ORR and DCR were 45

Peptide receptor radionuclide therapy (PRRT) using beta ( 177 Lu-DOTATATE) and alpha ( 225 Ac-DOTATATE) therapy seems to be a safe and effective treatment option for advanced gastroenteropancreatic (GEP) neuroendocrine tumors (NETs). However, treatment efficacy needs to be balanced with long-term outcomes and adverse events, especially in young patients with a longer life expectancy. Local therapy may be a more effective and safe option in achieving a cure in such cases. The index case shows the efficacy of endoscopic ultrasound (EUS)-guided ethanol ablation of residual metastatic lymph nodes in achieving a complete response after beta followed by alpha PRRT in a young patient.

Differentiated thyroid carcinoma (DTC) metastasizes frequently to lymph nodes, lungs, and bones; however, muscle metastasis is a very rare manifestation in DTC and has never been reported in poorly differentiated thyroid carcinomas (PDTCs). Whole-body iodine scans are done postsurgery for staging and iodine avidity at residual/metastatic sites in patients of thyroid cancer. Iodine-avid muscle deposits may mimic bone metastases on whole-body iodine-131 planar imaging. SPECT/CT plays an important role in the localisation of abnormal tracer activity. Moreover, the existing data on iodine avidity of PDTC is variable. We present a case with PDTC with multifocal radioiodine-avid muscle metastases mimicking as skeletal metastases.

INTRODUCTION:Cardiac MRI (CMR) and PET aid in early diagnosis and follow-up of cardiac sarcoidosis. 18 F-fluorodeoxyglucose ( 18 F-FDG) PET/computed tomography (CT) is a major criterion in diagnosing cardiac sarcoidosis disease activity and therapy response; however, requires stringent dietary modifications for suppressing myocardial uptake. 68 Ga-DOTANOC, targeting somatostatin receptors in sarcoid granulomas, maybe an alternative, showing minimal physiological myocardial uptake and not needing dietary modifications to suppress myocardial radiotracer activity. METHODOLOGY:This prospective study enrolled 23 patients, either biopsy-proven pulmonary sarcoidosis with suspected cardiac involvement or primary cardiac abnormalities with clinical and histopathological diagnosis from a systemic site. Patients underwent CMR, 13 N-NH 318 F-FDG PET/CT (post-low-carbohydrate, high-fat, high-protein diet), and 68 Ga-DOTANOC PET/CT. Patient-wise and cardiac-segment-wise analysis was done using Cohen's κ to assess intermodality agreement among three modalities. Mean maximum standardized uptake value (SUV max ) and target-to-background blood pool ratio (TBR) were calculated for positive lesions on 68 Ga-DOTANOC and 18 F-FDG PET/CT. RESULTS:68 Ga-DOTANOC and CMR showed almost perfect segment-wise agreement [Cohen's κ : 0.88, 95% confidence interval (CI): 0.84-0.92, P = 0.004] and moderate patient-wise agreement (Cohen's κ : 0.51, 95% CI: 0.29-0.73, P = 0.003). 18 F-FDG PET/CT and CMR showed almost perfect segment-wise agreement (Cohen's κ : 0.80, 95% CI: 0.76-0.84, P = 0.004) and substantial patient-wise agreement (Cohen's κ : 0.77, 95% CI: 0.58-0.96, P = 0.001). Mean lesion SUV max and TBR were similar for 68 Ga-DOTANOC (6.6 ± 2.8 and 3.4 ± 1.4) and 18 F-FDG (9.0 ± 5.4 and 3.6 ± 1.2) (unpaired t -test, P  = 0.16 for SUV max , P  = 0.68 for TBR). CONCLUSION:68 Ga-DOTANOC PET/CT shows promise as a complementary imaging modality for cardiac sacoidosis, with diagnostic performance comparable in many aspects to 18 F-FDG PET/CT and CMR. Further prospective studies are warranted to validate its role.

5095 Background: De-novo high-volume metastatic hormone-sensitive prostate cancer (mHSPC) presents a therapeutic challenge with a dismal five-year survival rate. Till recently, androgen deprivation therapy (ADT) with docetaxel had been the standard-of-care for such patients. Nevertheless, a substantial proportion of patients continue to harbour residual disease after completion of docetaxel. 177 Lu-PSMA-617 has shown positive survival outcomes in the metastatic castrate-resistant setting. Here, we intended to evaluate the role of upfront 177 Lu-PSMA-617 as consolidation therapy for residual disease following docetaxel in de-novo high-volume mHSPC patients. Methods: This was an investigator-initiated randomized, parallel-group, open-label, phase 2 trial. Patients with de-novo high-volume mHSPC who were initiated on ADT plus docetaxel (75 mg/m 2 /cycle x 6) and had residual non-progressive disease after completion of six cycles of docetaxel (defined as serum PSA >0.2 ng/mL with PSMA-positive disease on 68 Ga-PSMA-11 PET/CT) were randomized in 1:1 ratio to the experimental arm ( 177 Lu-PSMA-617, 7.4 GBq/cycle x 2, 6 weeks apart with continued ADT) or control arm (continued ADT only). The primary end-point was the proportion of patients achieving a serum PSA of ≤0.2 ng/mL at 6 months from randomization. Major secondary end-points included radiographic progression-free survival (rPFS), PSA-PFS, and treatment-emergent adverse events (TEAEs). A total sample size of 78 patients was estimated to be recruited assuming a 30% improvement in the primary end-point in the experimental arm with two-sided alpha of 5% and power of 80%. Results: The trial was terminated early due to poor accrual COVID-19 pandemic and following the change in standard of care from doublet to triplet therapy incorporating an androgen-receptor pathway inhibitor along with ADT plus docetaxel. Thirty high-volume mHSPC patients (15 in each arm) were recruited between January 2021 and May 2024. The primary end-point was achieved in 9/15 (60%) patients in the experimental arm versus 2/15 (13.3%) patients in the control arm (risk ratio: 4.5, 95% CI: 1.2-17.4, p=0.008). The median rPFS was 18 months in the experimental arm versus 9 months in the control arm, while the median PSA-PFS were 15 months and 9 months, respectively. No major grade 3/4 TEAEs were seen in the experimental arm. Conclusions: In de-novo high-volume mHSPC patients treated with docetaxel and having residual disease, 177 Lu-PSMA-617 consolidation therapy demonstrated remarkable efficacy in terms of biochemical response. Larger phase 3 trials are needed to definitively establish its survival benefits. Clinical trial information: CTRI/2021/01/030267 .

ABSTRACT:Prostate cancer frequently metastasizes to bones; however, the detection of metastases can be challenging in rare locations. We present the case of a 76-year-old man with metastatic castration-resistant prostate cancer with lymph nodal and skeletal metastases who underwent 177Lu-prostate-specific membrane antigen (PSMA) therapy. Initial 18F-PSMA PET/CT scan acquired until the midthigh failed to identify metastases in the foot, but posttherapy 177Lu-PSMA scan revealed the presence of metastases in the navicular and cuboid bones of the right foot, which is a very rare finding. This case highlights the limitations of standard PSMA PET/CT acquisition protocol and incremental value of whole-body posttherapy scan.

Prostate-specific membrane antigen (PSMA) overexpression on prostate cancer cells finally led to the FDA approval of the therapeutic use of 177 Lu-PSMA-617 in metastatic castrate-resistant prostate cancer. However, PSMA is also expressed in the neovasculature of other solid tumors, such as lung and renal cancer, making the theranostic potential of 177 Lu-PSMA-617 worth exploring in this setting. Here is such a case of an 83-year-old man with advanced non-small cell lung cancer where the theranostic potential of 177 Lu-PSMA-617 was explored using dosimetric analysis.

Introduction: Integrin antagonist complex (IAC), a novel alpha v beta 3 integrin antagonist peptidomimetic, has emerged as a promising agent for molecular imaging of tumor angiogenesis. This study evaluates the biodistribution and clinical efficacy of [Ga-68]Ga-DOTAGA-IAC PET/CT in detecting radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), comparing its diagnostic performance with [F-18]F-FDG PET/CT. Materials and Methods: In this prospective pilot study, RAIR-DTC patients underwent whole-body imaging with [F-18] F-FDG PET/CT, followed by [Ga-68]Ga-DOTAGA-IAC PET/CT. Biodistribution patterns of [Ga-68]Ga-DOTAGA-IAC were assessed. Lesions with abnormal, nonphysiologic tracer uptake (showing activity exceeding mediastinal blood pool) were considered positive for disease. Imaging findings were compared between the two modalities, and quantitative metrics, including SUVmax, metabolic tumor volume, and total lesion glycolysis, were analyzed statistically. Results: Among 30 patients with RAIR-DTC, [Ga-68]Ga-DOTAGA-IAC PET/CT revealed predominant physiological tracer uptake in the kidneys. [F-18]F-FDG PET/CT identified 97 lesions, predominantly nodal (73.2%), while [Ga-68]Ga-DOTAGA-IAC PET/CT detected 34 lesions, 50% of which were nodal. Few patients exhibited multiple lesions with varying uptake grades, with 20% showing coexisting higher-grade lesions (grade II or above) on [Ga-68]Ga-DOTAGA-IAC PET/CT. Conclusion: Angiogenesis imaging using [Ga-68]Ga-DOTAGA-IAC PET/CT demonstrates limited sensitivity for lesion detection in patients with RAIR-DTC compared with [F-18]F-FDG PET/CT. However, the potential of [Ga-68]Ga-DOTAGA-IAC as a diagnostic tool for other cancers has been used in other cancers with positive imaging characteristics warranting further exploration.

Diaphragmatic eventration is the elevation of hemi-diaphragm without any disruption to diaphragmatic continuity which can be congenital or acquired. The most common acquired cause is phrenic nerve paralysis due to traumatic causes and is usually incidentally diagnosed on chest radiograph or computed tomography. We hereby report a case of a patient who had road traffic accident with fracture of the left proximal femur. Stress Myocardial Perfusion Imaging (MPI) done for pre-operative clearance showed an incidental tracer avidity adjoining to left myocardium in the thorax. It was confirmed on anatomical imaging to be gastric cavity uptake due to diaphragm eventration.

177Lu-DOTATATE has emerged as a viable treatment strategy for advanced well-differentiated grade 1/2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Few retrospective studies have shown concomitant 177Lu-DOTATATE with radiosensitizing low-dose capecitabine to be effective in advanced NETs. However, this has not been validated in prospective randomized-controlled trials. Methods: In this investigator-initiated, parallel-group, open-label, phase 2 trial, patients with grade 1/2 GEP-NETs, having progressive somatostatin receptor- positive, locally advanced, or metastatic disease on 68Ga-DOTANOC PET/CT, were randomly assigned in a 1:1 ratio to 177Lu-DOTATATE plus capecitabine (experimental arm) or 177Lu-DOTATATE only (control arm). 177Lu-DOTATATE was administered at approximately 7.4 GBq/cycle intravenously, for up to 4 cycles, at 8 wk intervals, whereas capecitabine was given at 1,250 mg/m2/d orally from day 0 to day 14 of each cycle of 177Lu-DOTATATE. The primary endpoint was the objective response rate. Secondary endpoints included the disease control rate, progression-free survival, overall survival, and adverse events. Results: Seventy-two patients (median age, 53 y; range, 18-79 y) were enrolled. The objective response rate was 33.3% (95% CI, 18.6- 50.9%) in the experimental arm versus 30.6% (95% CI, 16.4-48.1%) in the control arm (P = 0:800). The disease control rate was 88.9% (95% CI, 73.9-96.9%) and 91.7% (95% CI, 77.5-98.2%) in the experimental and control arms, respectively (P = 1.000). The estimated median progression-free survival in the experimental arm was 29 mo (95% CI, 22-29 mo) versus 31 mo (95% CI, 29-32 mo) in the control arm (P = 0.401). The median overall survival was not reached in either arm (P = 0.876). Overall, adverse events of at least grade 3 were noted in 7 patients in the experimental arm versus 6 patients in the control arm (P = 0.759). Conclusion: Based on the results of this trial, the addition of low-dose capecitabine to 177Lu-DOTATATE in advanced grade 1/2 GEP-NETs did not lead to superior radiographic responses. Further studies are needed to evaluate its potential role in high-grade NETs.

PURPOSE:Patients with metastatic castration-resistant prostate cancer (mCRPC) often undergo multiple treatments, making accurate response assessment vital. The conventional imaging-based PCWG3 criteria, incorporating the RECIST-1.1, have been the gold standard so far. Although 68Ga-PSMA-11-PET/CT has shown an incremental role in staging of prostate cancer, its utility in response evaluation lacks prospective validation. Here, we prospectively evaluate different 68Ga-PSMA-11-PET/CT-based response evaluation criteria, including RECIP-1.0, PPP, and aPERCIST, and compare these with the PCWG3 criteria. METHODS:mCRPC patients, initiating treatment with taxanes, androgen-receptor pathway inhibitors (ARPIs), or 177Lu-PSMA-617, underwent 68Ga-PSMA-11-PET/CT and conventional imaging (CECT and bone scintigraphy) at baseline, and every 12 weeks after treatment. RESULTS:Thirty-four mCRPC patients were included (median age: 68.5 y, median PSA: 61.9 ng/mL). Nonprogression rates at 12 weeks according to PCWG3, aPERCIST, PPP, and RECIP-1.0 were 23.5%, 8.8%, 17.6%, and 23.5%, respectively. The highest inter-reader agreement was observed with RECIP-1.0 (κ=0.84). The median OS was 16.5 months with nonprogression according to PCWG3 being associated with significantly better OS (P=0.02), and no significant associations were observed with the rest of the criteria. In surrogacy analysis of rPFS for OS in the overall cohort, the highest C-index was observed for PCWG3-rPFS (C=0.72), followed by RECIP-rPFS (C=0.71). In subgroup analyses, RECIP-rPFS had the highest C-index for non-ARPI patients (C=0.76), and PCWG3-rPFS for the ARPI patients (C=0.75). CONCLUSIONS:PCWG3 remains the most effective response criterion overall and for ARPI-treated patients, while RECIP-1.0 showed better prognostic value for non-ARPI patients. Larger studies are needed to validate these findings.

Metastasis from differentiated thyroid cancer frequently occurs in regional lymph nodes, followed by the lungs and bones. However, mandibular metastases related to thyroid carcinoma are exceedingly rare and may represent the sole manifestation of an undiagnosed underlying malignancy. This study aims to analyze the presentation, management, and survival outcomes in a case series of differentiated thyroid carcinoma patients having mandibular metastasis.

BACKGROUND:Coronary microvascular dysfunction is implicated in ∼two-thirds of ischaemia with no obstructive coronary artery disease (INOCA) cases and is significant due to its association with a higher risk of major adverse cardiac events (MACE). While invasive techniques are the gold standard for diagnosing coronary microvascular dysfunction (CMD), positron emission tomography (PET) offers a noninvasive approach to quantifying myocardial blood flow (MBF) and detecting CMD. This study aimed to quantify myocardial flow reserve (MFR) using PET in INOCA patients to identify CMD and to correlate it with thrombolysis in myocardial infarction (TIMI) and TIMI myocardial perfusion grade (TMPG) angiographic flow grades. METHODS:Thirty INOCA patients with angiographic evidence of non-obstructive coronaries and slow flow were prospectively enrolled and underwent dynamic rest and stress cardiac 13N-NH3 PET with MBF and MFR quantification. Patients with MFR values below 2.3 were classified as having CMD. Angiographic flow grades (TIMI and TMPG) were correlated with MFR and MBF. RESULTS:The mean global stress MBF and MFR for the study cohort were 2.54 ± 0.72 mL/minute/gm and 2.91 ± 0.81, respectively. No significant correlation was found between MFR and TIMI (r = -0.140, P = 0.108) or MFR and TMPG (r = -0.06, P = 0.446). Among the participants, 8 (27 %) had reduced global MFR less than 2.3 (mean: 1.80 ± 0.36), indicating CMD. The remaining 22 patients (73 %) had normal MFR values. Within the CMD group, 3 patients had functional CMD with elevated resting MBF, while 5 had classic CMD with blunted hyperaemic response to vasodilator stress. CONCLUSIONS:PET is an excellent noninvasive modality for diagnosing CMD. Coronary slow flow in angiographically normal arteries does not correlate with 13N-NH3 PET MFR values and is not a reliable marker for identifying CMD as indicated by the study's findings.