Somatostatin Receptor Targeted PET-CT and Its Role in the Management and Theranostics of Gastroenteropancreatic Neuroendocrine Neoplasms.

Somatostatin receptor (SSTR) agonist-based Positron Emission Tomography-Computed Tomography (PET-CT) imaging is nowadays the mainstay for the assessment and diagnostic imaging of neuroendocrine neoplasms (NEN), especially in well-differentiated neuroendocrine tumors (NET) (World Health Organization (WHO) grade I and II). Major clinical indications for SSTR imaging are primary staging and metastatic workup, especially (a) before surgery, (b) detection of unknown primary in metastatic NET, (c) patient selection for theranostics and appropriate therapy, especially peptide receptor radionuclide therapy (PRRT), while less major indications include treatment response evaluation on and disease prognostication. Dual tracer PET-CT imaging using SSTR targeted PET tracers, viz. [68Ga]Ga-DOTA-Tyr3-Octreotate (DOTA-TATE) and [68Ga]Ga-DOTA-NaI3-Octreotide (DOTA-NOC), and fluorodeoxyglucose (FDG), have recently gained widespread acceptance for better assessment of whole-body tumor biology compared to single-site histopathology, in terms of being non-invasive and the ability to assess inter- and intra-tumoral heterogeneity on a global scale. FDG uptake has been identified as independent adverse risk factor in various studies. Recently, somatostatin receptor antagonists have been shown to be more sensitive and specific in detecting the disease. The aim of this review article is to summarize the clinical importance of SSTR-based imaging in the clinical management of neuroendocrine and related tumors.

PSMA Receptor-Based PET-CT: The Basics and Current Status in Clinical and Research Applications.

Prostate-specific membrane antigen (PSMA) is a 100 kD, 750 amino acid (AA) long type II transmembrane glycoprotein that has a short N-terminal intracellular domain with 19 AA, 24 AA transmembrane proteins and a large C-terminal extracellular domain with 707 AA. PSMA has been mapped to chromosome 11p 11-12 in the region of the folate hydrolase gene (FOLH1) and has no known natural ligand. The protein possesses enzymatic activity-glutamate carboxypeptidase II (GCP-II)-and is thought to have role in folate uptake (FOLH1 gene). 'PSMA' expression, although significantly up-regulated in prostate carcinoma (more in high-risk and aggressive variants), is not exclusive for it and is noted in various other benign and malignant conditions, especially in the neovasculature. Currently, PSMA PET-CT is approved for high-risk and biochemically recurrent prostate carcinoma (PCa), and in patient selection for PSMA based theranostics. This review aims to highlight the clinical evolution of the PSMA molecule and PSMA PET-CT as a diagnostic modality, various indications of PSMA PET-CT, the appropriateness criteria for its use, pitfalls and artefacts, and other uses of PSMA PET apart from prostate carcinoma.

Comparison of Local and Intravenous Zoledronic Acid on Histopathology and Recurrence Rate after Extended Curettage in Giant Cell Tumors of Proximal Tibia: A Prospective Study.

Introduction: The bone pathology-giant cell tumor (GCT) is a locally aggressive and recurrent lesion. A bisphosphonate-zoledronic acid (ZA) has been known to lower the recurrence and resorption in similar bone lesions. Hence, we evaluated the effectivity of the ZA for the GCT of the proximal tibia. Materials and Methods: We piloted a prospective clinical observational study. We included 100 subjects with GCT, who were divided into two equal groups of case (given ZA) and control (no ZA). The histopathological features and the recurrence rates along with other findings were compared with P < 0.05 deliberated as significant. Results: We observed that for in the case group, calcification and fibrosis that were beneficial were observed. Reduced giant cells and lower recurrence rate are seen in the case group. No significant variation in the functional outcome was seen between the groups. Conclusions: ZA was shown to have beneficial effect on the outcome for the treatment of the GCT.

Clinicoradiological Comparison of Outcomes of LRS Fixator and Ilizarov in Infected Nonunion of Tibia Based on Bone Gap Quantification: An Original Research.

Introduction: The surgery of the fracture of the long bones is inherent to certain complications, one being nonunion. As various modalities are proposed, we aim in our study to compare the clinical and radiographic outcomes after the treatment with the Limb Reconstruction System (LRS) fixator and Ilizarov for the infected tibia with nonunion considering the bone gap quantifications. Materials and Methods: We conducted an observational prospective study among 40 subjects with tibial nonunion. They were grouped equally to be treated by the LRS fixator and Ilizarov. Clinical and radiographic outcomes were compared using the "Chi-squared and independent Student's t-test," deliberating P < 0.05 as significant. Results: We observed no significant difference for both the groups in the clinical union and functional and radiographic outcome for the various gaps of the nonunion. There was no significant difference for the groups when the time of healing was compared. Conclusion: Comparable results are seen for both the treatment modalities. However, IL fixator performed better clinically, while the LRS was easily accepted by the patients.

Dual-Tracer PET-Computed Tomography Imaging for Precision Radio-Molecular Theranostics of Prostate Cancer: A Futuristic Perspective.

Dual/multi-tracer PET-computed tomography (CT) scan has been an interesting and intriguing concept and is promising in noninvasive and overall characterization of tumor biology and heterogeneity and has scientifically augmented the practice of precision oncology. In prostate carcinoma, particularly in metastatic castration-resistant prostate carcinoma setting, dual-tracer PET-CT can be potentially useful in selecting patients for chemotherapy, androgen deprivation therapy or prostate-specific membrane antigen (PSMA)-based peptide receptor radioligand therapy either as mono-therapy or as combination therapy, ascertaining differentiation status, staging/restaging, prognostication, and predicting progression/response. PSMA PET/CT has great potential as a "rule out" test in baseline staging, while being very useful in restaging and metastatic workup.

An Appraisal and Update of Fluorodeoxyglucose and Non-Fluorodeoxyglucose-PET Tracers in Thyroid and Non-Thyroid Endocrine Neoplasms.

Endocrine neoplasms and malignancies are a diverse group of tumors with varied clinical, histopathologic, and functional features. These tumors vary from sporadic to hereditary, isolated entities to multiple neoplastic syndromes, functioning and non functioning tumors, unifocal locally invasive, and advanced to multifocal tumors with disseminated distant metastases. The presence of various specific biomarkers and specific receptor targets serves as valuable tools for diagnosis, prognosis, and management. PET-CT with FDG and a multitude of novel and specific radiotracers towards specific therapeutic targets mandates personalization of their use, so as to ensure maximum clinical benefit in the management of these neoplasms.

Discordance Between Histopathologic Grading and Dual-Tracer PET/CT Findings in Metastatic NETs and Outcome of 177Lu-DOTATATE PRRT: Does In Vivo Molecular PET Perform Better from the Viewpoint of Prediction of Tumor Biology?

Discordance between histopathologic grading and dual-tracer PET/CT (68Ga-DOTATATE and 18F-FDG) findings in neuroendocrine tumors (NETs), though not typical, can be encountered in real-world scenarios. The aim of this study was to assess patients with discordance between World Health Organization (WHO) 2017 grade-predicted molecular PET/CT imaging and the actual dual-tracer PET/CT findings (by exploring their histopathologic, immunohistochemical, and molecular imaging characteristics), with a view toward identifying the prognostic determinants affecting outcome in a peptide receptor radionuclide therapy setup. Methods: Thirty-six patients with histopathologically proven inoperable, locally advanced or metastatic NETs, referred for peptide receptor radionuclide therapy, were included in this study. The cohort was divided into 2 broad population groups: those with discordance (between WHO 2017 grade-predicted molecular imaging and the dual-tracer PET/CT findings) and control (showing both 18F-FDG and 68Ga-DOTATATE uptake). The cohort was divided on the basis of dual-tracer PET/CT into 3 groups: metabolically inactive (non-18F-FDG-avid) and somatostatin receptor (SSTR)-expressing tumors, metabolically active (18F-FDG-avid) and non-68Ga-DOTATATE-concentrating (non-SSTR-expressing) tumors, and matched imaging characteristics with the WHO 2017 grading system (showing both 18F-FDG- and 68Ga-DOTATATE-concentrating disease) for statistical analysis. Descriptive statistics were used to analyze categoric data; multivariate analysis was used to assess the correlation between different variables with progression-free survival (PFS) and overall survival (OS). Kaplan-Meier curves were used for survival analysis to calculate median survival and to analyze survival on the basis of WHO 2017 grading and dual-tracer PET. Cox proportional hazards regression analysis was used to determine predictors of survival (OS and PFS). Results: Of the 36-patient cohort, 24 (66.7%) showed discordance and 12 (33.3%) were in the control group. Among those showing discordance: 14 (38.9%) had metabolically inactive and SSTR-expressing disease and the remaining 10 (27.8%) had 18F-FDG-concentrating and non-SSTR-expressing disease. Among those in the control group, 12 (33.3%) had intermediate-grade NETs and showed matched (68Ga-DOTATATE- and 18F-FDG-concentrating lesions) disease. Multivariate analysis in patients with discordant findings showed a significant correlation of dual-tracer PET with OS, whereas no significant correlation could be established between WHO grade and OS in the discordant subgroups. No significant correlation could be appreciated between PFS and either dual-tracer PET or WHO grading. The Kaplan-Meier analysis and Cox analysis showed dual-tracer PET/CT imaging to be a significant prognostic determinant and predictor of outcome, respectively. Conclusion: In NET patients with discordance between the 2 parameters, dual-tracer PET/CT with 18F-FDG and 68Ga-DOTATATE performed better than WHO grading, differentiation status, and immunohistochemistry in prognosticating and predicting outcome.

Concept proposal for a six-tier integrated dual tracer PET-CT (68Ga-PSMA and FDG) image scoring system ('Pro-PET' score) and examining its potential implications in metastatic castration-resistant prostate carcinoma theranostics and prognosis.

OBJECTIVES: To develop and examine a scoring system in metastatic castration-resistant prostate carcinoma (mCRPC) that integrates findings of both 68Ga-prostate-specific membrane antigen (PSMA) and flurodeoxyglucose (FDG) PET-CT imaging in a single combined parameter and referred to as the 'Pro-PET' score. METHODS: A six-tier integrated dual tracer PET-CT (68Ga-PSMA and FDG) Image Scoring System ('Pro-PET' score) was conceptualized, based on the findings of both 68Ga-PSMA-11 and FDG PET-CT in patients of mCRPC. This proposed integrated scoring was examined in a retrospective analytical study assessing mCRPC patients (n = 47) referred for 177Lu-PSMA-617 peptide receptor radioligand therapy (PRLT) and had both FDG and 68Ga-PSMA PET-CT undertaken within 15 days of each other without any interim treatment intervention. The 'Pro-PET' score grades and subgrades were assigned and compared with clinical data, such as histopathology, Gleason score, serum prostate-specific antigen (PSA), treatment response (symptomatic, biochemical, metabolic and anatomical) and survival [overall survival (OS) and progression-free survival (PFS)]. RESULTS: The Pro-PET score significantly correlated with symptomatic (P = 0.05), biochemical (P = 0.05), metabolic (P = 0.001) and anatomical (P = 0.012) responses, PFS (P = 0.03) and OS (P = 0.027). On multivariate analysis, histopathology, Gleason score and PSA as individual parameters were not significantly associated with OS and PFS, whereas the Pro-PET score was found to have a significant association (P = 0.001 for PFS and 0.011 for OS). CONCLUSION: The 'Pro-PET' scoring system integrating dual tracer PET-CT imaging findings in a single parameter appeared as a potentially promising prognostic marker that has the potential to enhance the objectivity and scientific basis of prostate carcinoma theranostics and prognostication.

Examining Absorbed Doses of Indigenously Developed 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer Patients at Baseline and During Course of Peptide Receptor Radioligand Therapy.

Aim: The objective of this study was to estimate the absorbed doses to the normal organs and tumor lesions in metastatic castration-resistant prostate cancer (mCRPC) patients treated with indigenously developed 177Lu-PSMA-617 that could establish optimal treatment protocol with minimum risk to the dose-limiting organs. Furthermore, attempt was also made to compare radiation absorbed doses for normal organs and tumor lesions in subsequent cycles of 177Lu-PSMA-617 peptide receptor radioligand therapy (PRLT) in the same group of patients during the course of treatment. Methods: A total of 30 patients of proven mCRPC were enrolled for this prospective study. These patients received up to 5 cycles of treatment with 177Lu-PSMA-617 PRLT (1 cycle for 13 patients, 2 cycles for 9 patients, 3 cycles for 3 patients, and 5 cycles for 5 patients), at 11-12-week intervals between the two successive therapies. The patients underwent postadministration whole-body scintigraphy at five time points: 0.5 (prevoid), 2, 12, 24, and 72/96 h (postvoid). From time-activity curves generated by drawing regions of interests on the images, number of disintegrations was determined. Tumor masses were estimated from pretherapeutic 68Ga-PSMA-11 positron emission tomography-computed tomography images. Absorbed doses for organs and tumors were calculated using OLINDA 2.0 software. Results: The average activity of 177Lu-PSMA-617 (mean ± SD) administered per patient per cycle was 4.94 ± 0.45 GBq. The mean absorbed organ doses (mean ± SD) from first therapy cycle in Gy/GBq were as follows: kidneys 0.52 ± 0.16, spleen 0.17 ± 0.07, liver 0.08 ± 0.05, salivary glands 0.53 ± 0.30, lacrimal glands 1.45 ± 0.85, nasal mucosa membrane 0.46 ± 0.19, urinary bladder 0.23 ± 0.02, and bone marrow 0.04 ± 0.03. The mean effective dose for whole body from first therapy cycle was 0.05 ± 0.03 Sv/GBq. Among all the normal organs, lacrimal glands received the highest absorbed dose. The median dose for all lesions, bone lesions, lymph nodes, primary site, liver lesion, lung lesion, and soft tissue deposit from first therapy cycle was determined to be 4.17, 4.23, 3.96, 4.36, 10.27, 0.78, and 4.68 Gy/GBq respectively. Absorbed doses received by the normal organs in five consecutive cycles follow three different trends, (a) for kidneys, salivary glands, and nasal mucous membrane, absorbed doses increased from first therapy cycle to second therapy cycle and then slowly decreased in subsequently therapy cycles; (b) for spleen, liver, and lacrimal glands, absorbed doses decreased with the successive therapy cycles; and (c) in case of bone marrow, bladder, and whole body, mean absorbed dose almost remained constant in each therapy cycle. Absorbed doses to the lesions gradually decreased with increase of the number of therapy cycles. Conclusions: The organ and tumor absorbed doses of 177Lu-PSMA-617 in mCRPC patients were found to be comparable to the data reported in the literature. The highest absorbed organ dose was observed in lacrimal glands and being a dose limiting organ, a cumulative activity up to 32.5 GBq (878 mCi) of 177Lu-PSMA-617 in 4-5 therapy cycles appears safe and feasible to achieve full therapeutic window.

Combined 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy and Platinum-Based Chemotherapy in Recurrent, Metastatic Sinonasal Neuroendocrine Carcinoma: A Promising Therapeutic Option.

Sinonasal neuroendocrine carcinomas (SNCs), in contrast to neuroendocrine carcinomas at other sites, are notorious for their recurrent and locally aggressive nature. The clinical concern is primarily due to their complex anatomy and close proximity to vital structures, compounded by lack of proper understanding of pathogenesis, no definitive classification or staging system, and no established treatment guidelines. We present the promise of combined treatment with 177Lu-DOTATATE-based peptide receptor radionuclide therapy (PRRT) and platinum-based chemotherapy in a patient with high-grade, recurrent, and metastatic SNC (that demonstrated high uptake on both 68Ga-DOTATATE and 18F-FDG PET/CT), which showed a significant partial response. The case report highlights the feasibility and effectiveness of applying a combined protocol of 177Lu-DOTATATE and platinum-based chemotherapy in the management of high-grade, recurrent, metastatic SNC.

Comparison of Dual-Tracer PET and CT Features to Conventional Risk Categories in Assessing Response to 177Lu-PSMA-617 Therapy for Metastatic Prostate Adenocarcinoma with Urinary Bladder Involvement.

The present communication details the imaging characteristics, peculiarities, and response to 177Lu-labeled prostate-specific membrane antigen (PSMA)-617-targeted radioligand therapy (PRLT) in accordance with Gleason score and use of dual-tracer PET (68Ga-PSMA-11 and 18F-FDG) in patients with urinary bladder invasion or metastasis by prostate cancer, including the prognostic value of 18F-FDG PET in predicting response to treatment. The CT attenuation units (Hounsfield units) correlated with the prostate primary in the case of direct tumor extension from the prostate, whereas in hematogenous metastatic seeding the Hounsfield units were lower than in the primary prostatic tumor. A favorable outcome to 177Lu-PSMA-617 PRLT was observed in patients with low or no baseline 18F-FDG uptake despite a high Gleason score and a high-risk National Comprehensive Cancer Network prognostic category and did not correlate with the latter alone, whereas a high SUVmax on 18F-FDG PET/CT was associated with an adverse outcome. These findings suggest a promising role for 18F-FDG PET/CT in predicting therapeutic outcomes more confidently, and hence the concept of dual-tracer PET appears to hold good in prostate adenocarcinoma theranostics.

Rare-Site Primary Soft-Tissue Neuroendocrine Tumor with Metastases and Near-Complete Resolution with 177Lu-DOTATATE: Documenting a Promising Clinical Application of Peptide Receptor Radionuclide Therapy.

Neuroendocrine tumors (NETs) of the skin or soft tissue are rare (mostly described as sites of metastasis), whereas primary soft-tissue NETs are extremely rare; they are usually diagnosed at advanced stages with distant metastases because of their indolent nature. We herein describe our experience with 2 such cases. In the first case, the NET originated in the retroperitoneal soft tissue, and in the second case, the patient was a middle-aged lady with NET arising from soft tissue in the pelvis. Both patients were treated with 177Lu-DOTATATE in view of their somatostatin receptor-expressing metastatic lesions, demonstrating an excellent outcome as reflected by a complete metabolic response and near-complete anatomic response to the administered peptide receptor radionuclide therapy. The noteworthy factors of the reported cases were, first, unusual sites of primary tumor and, second, near-complete to complete symptomatic, anatomic, and metabolic resolution of the recurrent primary tumor and metastatic lesions with peptide receptor radionuclide therapy alone. NETs arising from rare anatomic locations are usually nonfunctioning, with good clinical outcomes, and 177Lu-DOTATATE peptide receptor radionuclide therapy can be considered promising in patients with metastatic or advanced disease.

Metastatic or locally advanced mediastinal neuroendocrine tumours: outcome with 177Lu-DOTATATE-based peptide receptor radionuclide therapy and assessment of prognostic factors.

BACKGROUND: Primary neuroendocrine tumours (NETs) of mediastinum are unusual tumours with aggressive biological behaviour with limited treatment options and guarded prognosis. METHODS: Twenty-seven patients with histopathologically and radiologically proven metastatic or advanced mediastinal NET, who had undergone 177Lu-DOTATATE PRRT, were included in this retrospective analysis. Descriptive statistics was employed to calculate the cumulative overall survival (OS) and progression-free survival (PFS), determining correlation and strength of correlation between different variables with OS and PFS and finally, predictors of outcome (OS and PFS). RESULTS: In all 27 patients enrolled and analyzed, complete symptomatic response was observed in 10 patients (37%), partial response in seven patients (25.9%), symptomatically stable disease in four patients (14.8%), and symptoms progressed or worsened in six patients (22.2%). Metabolic response evaluation demonstrated complete metabolic response in one patient (3.7%), partial metabolic response was seen in nine patients (33.3%), metabolically stable disease was seen in five patients (18.5%), and 12 patients (44.4%) showed metabolic disease progression. None of the patients achieved complete anatomical/morphological response, six (22.2%) showed partial response, seven (25.9%) showed stable disease, and in 14 patients (51.9%), there was morphological disease progression. At the time of analysis, 10 patients (37%) succumbed to the disease. The median PFS was 36 months and the median OS was 66 months. Bivariate analysis showed significant level of association of PFS with surgical intervention, higher cumulative PRRT dose, metabolic response, smaller sized primary lesion, and low lesional FDG uptake. With regard to OS, higher cumulative PRRT dose, low FDG uptake and longer PFS showed significant association. CONCLUSION: Previous surgical intervention (including debulking surgery with R1 resection), higher cumulative dose of PRRT, and low FDG uptake of the tumour are associated with prolonged OS and PFS in patients with metastatic or advanced mediastinal NETs and were independent favourable prognostic markers.

Biodistribution and Dosimetry of Indigenously Produced 131I-Rituximab in B-Cell Lymphoma: Pilot Study Estimating Patient-Specific Dose Comparing 2 Different Dosimetric Methods.

Cost containment through indigenous production of radioimmunotherapy agents for non-Hodgkin lymphoma (NHL) would be a pivotal step toward wider clinical availability, especially in developing countries. We examined the biodistribution and dosimetry of indigenously developed and radiolabeled 131I-rituximab, using the monoclonal antibody of chimeric origin, in patients with B-cell lymphoma for potential use in radioimmunotherapy. Methods: This prospective study included 13 patients with B-cell NHL who underwent low-dose diagnostic scanning for dosimetric and biodistribution studies. Soon after rituximab infusion, a diagnostic dose of radioiodinated rituximab was administered. Serial planar whole-body γ-camera images were taken soon afterward and on days 1, 2, 4, and 6. A source of 131I with known activity was used as a reference standard for dosimetry calculations. Results: The patient-specific administered dose that would give a whole-body absorbed radiation dose of 75 cGy, calculated by the MIRD schema, ranged from 3,095.42 to 6,330.33 MBq (83.66-171.09 mCi), with a mean of 3,986.01 ± 863.95 MBq (107.73 ± 23.35 mCi) and a median of 3,697.41 MBq (99.93 mCi). The mean residence time was 69.54 h. Within the first 48 h at least 50% of the injected activity was cleared, and by 144 h at least 80% was cleared. The patient-specific administered dose that would give a whole-body absorbed radiation dose of 75 cGy, calculated by mean residence time and activity-hours, ranged from 2,654.75 to 6,210.45 MBq (71.75-167.85 mCi), with a mean of 3,576.42 ± 927.59 MBq (96.66 ± 25.07 mCi) and a median of 3,421.02 MBq (92.46 mCi). With respect to organ-specific dosimetry, the mean absorbed doses to organs (apart from blood pool [3.77 Gy] and spleen [4.02 Gy]) were 0.97 Gy to the lungs, 0.69 Gy to the liver, and 0.7 Gy to the kidneys. Conclusion: The indigenous product had kinetics similar to commercial radiopharmaceuticals, with the advantage of a lower human antimouse antibody response because of the pharmaceutical's being a chimeric antibody rather than a murine antibody. Hence, clinical administration was safe. In none of the organs did dose-limiting radiation exposure occur at the proposed therapeutic dose.

Implications of fluorodeoxyglucose uptake in low-intermediate grade metastatic neuroendocrine tumors from peptide receptor radionuclide therapy outcome viewpoint: A semi-quantitative standardized uptake value-based analysis.

Dual tracer positron emission tomography (PET) imaging approach (with 68Ga-DOTATATE PET-computed tomography (CT) for somatostatin receptor and 18-fluorodeoxyglucose (18FDG) PET-CT for glucose transporter receptor) plays a vital role in baseline differentiation, treatment decision-making, and prognostic assessment of neuroendocrine tumors (NETs). The aims of this study were to observe and compare the clinical behavior of low-/intermediate-grade NETs depending on their baseline FDG metabolism (calculated through pre-peptide receptor radionuclide therapy [PRRT] FDG standardized uptake value [SUV]) and to determine its prognostic importance in predicting extent of therapeutic response (post-PRRT) in terms of symptomatic, biochemical, and scan parameters along with the long-term impact on progression-free survival (PFS) and overall survival (OS). Fifty-nine patients with low (≤2%) and intermediate (3-20% Mib-1/Ki-67 index) grade metastatic NET were selected for this retrospective analysis and divided into three groups: Group 1 consisted of patients having low-grade FDG uptake at baseline, predefined as SUVmax< 5 (n = 13); Group 2 consisted of those having intermediate-grade FDG uptake at baseline, SUVmax5-10 (n = 34), and Group 3 consisted of patients having high-grade FDG uptake at baseline, defined as SUVmax>10 (n = 12). The trend of FDG avidity was studied from the baseline till the time of analysis and the overall outcomes were compared in terms of symptomatic response (Karnofsky and ECOG performance score), biochemical response, scan response (anatomical and metabolic, RECIST 1.1 and PERCIST 1.0), PFS and OS. Patients in Groups 1 and 2 showed highest proportion of symptomatic complete response, biochemical partial response, and stable disease on scan. These patients also demonstrated better PFS and OS and lowest hazard ratio compared to patients in the Group 3. An important finding was a substantial fraction of the complete metabolic responders (CMRs) across the groups, achieved CMR within first 2 cycles of PRRT (85% of Group 1, 51% of Group 2, and 47% of Group 3). In conclusion, most of the patients of low-/intermediate-grade NET having low-to-moderate baseline tumor FDG metabolism (SUVmax≤10) showed favorable symptomatic response with good biochemical and anatomical disease control and were associated with prolonged PFS and OS, compared to that of those having high-grade baseline tumor FDG metabolism (SUVmax>10).