Neuroendocrine tumors (NETs) are a rare and heterogeneous class of neoplastic lesions, but their prevalence has increased significantly over the past three decades. These tumors are aggressive and difficult to treat. Improving diagnostic efficiency and treatment effectiveness is important for patients with neuroendocrine tumors. Radiopharmaceutical therapeutic diagnostics combines diagnosis and treatment technology and has broad prospects in precision medicine, especially for the early diagnosis and treatment of tumors. To compare the diagnostic advantages of radiolabeled somatostatin receptor agonists and antagonists for liver metastases from NETs and the disease control rate in NET patients. Systematic search of PubMed, Embase, Cochrane, Ovid, Scopus, and Web of Science databases up to 29 October 2024. Clinical trials of somatostatin receptor agonists and antagonists for NET diagnosis or treatment. Following PRISMA guidelines, data were independently extracted by two researchers. Pooled diagnostic or treatment effects and 95% CIs were reported using a random-effects meta-analysis model. Effect of somatostatin receptor agonists and antagonists in detecting liver metastases and disease control rate. Risk Ratio (RR) for liver metastasis detection and Effect Size (ES) for disease control rate were calculated. From 5291 articles, 52 were included in the meta-analysis. Radiolabeled somatostatin receptor antagonists were significantly more effective than agonists in detecting liver lesions (RR = 11.57, 95% CI: 4.10, 32.67). Disease control rates were higher with antagonists (ES = 0.90, 95% CI: 0.83, 0.96) compared to agonists (ES = 0.82, 95% CI: 0.78, 0.85, z = 2.12, p = 0.03). Radiolabeled somatostatin receptor antagonists outperform agonists in diagnosing hepatic lesions and controlling disease in NETs, highlighting their clinical superiority. This meta-analysis provides critical insights into the diagnostic and therapeutic efficacy of somatostatin receptor antagonists, and may offer a potential paradigm shift in the management of neuroendocrine tumors. Nevertheless, the smaller number of studies on antagonists may limit the generalizability of the findings and underscore the need for further clinical trials to validate these results.

This retrospective analysis interrogates the value of a multimodal biomarker paradigm to characterize molecular and clinical responses to [²²⁵Ac]Ac-PSMA-617-targeted α-therapy (TAT) in cohorts of heavily pretreated metastatic castration-resistant prostate cancer patients who had shown limited benefit from prior [¹⁷⁷Lu]Lu-PSMA-617. By integrating quantitative PSMA-PET/CT metrics—notably total tumor volume (TTV) and lesion SUV indices—with longitudinal PSA kinetics, routine hematologic and biochemical markers, and semiquantitative assessment of salivary gland uptake, we sought to delineate treatment effect, organ-specific off-target impact, and prognostic biomarker signatures. In twelve patients receiving 2–6 cycles of therapy (median activity 8 MBq), biochemical responses were frequent: 8/12 experienced PSA declines and 5/12 achieved ≥50% reduction. Concordant molecular responses were observed on PSMA-PET, with SUV_peak-based partial response in 7/12, stable disease in 3/12, and progressive disease in 2/12 of the target lesions. Qualitative concordance between TTV and PSA response was observed in four illustrative patients; no formal cohort-level concordance analysis was performed. Notably, salivary gland tracer uptake on [⁶⁸Ga]Ga-PSMA-11 PET/CT decreased after two cycles of [²²⁵Ac]Ac-PSMA-617 compared with baseline (SUV_max −63.7%; SUV_mean −45.5%). In this exploratory cohort, elevations in PSA, alkaline phosphatase, and LDH measured after two cycles of therapy, along with low hemoglobin, platelet count, and creatinine, were associated with shorter overall survival. Median progression-free survival and overall survival were 27 and 53 weeks, respectively. Collectively, these findings suggest that a combined PSMA-PET TTV–PSA–blood biomarker framework may offer complementary insight alongside PSA alone for characterizing therapeutic response, although its incremental value over PSA was not formally tested in this exploratory cohort; blood-based biomarkers (PSA, ALP) showed the most consistent prognostic association with survival, providing objective measures of both tumor response and collateral tissue impact. Prospective validation in larger, controlled cohorts is warranted to refine biomarker thresholds and guide personalized TAT strategies.

This study evaluates the efficacy and safety of [²²⁵Ac]Ac-PSMA-617 targeted alpha therapy (TAT) in patients with metastatic castration-resistant prostate cancer (mCRPC) who demonstrated Prostate-Specific Antigen (PSA) based non-responsiveness to prior [¹⁷⁷Lu]Lu-PSMA-617 therapy. Moving beyond traditional PSA-level assessments, we integrate blood biomarkers, PSMA-PET based total tumor volume (TTV) and salivary glands uptake. This retrospective analysis provides a comprehensive framework for evaluating treatment efficacy. Twelve patients underwent 2–6 cycles of [²²⁵Ac]Ac-PSMA-617, with a median activity of 8 MBq. PSA decline was observed in 8/12 patients, with 5/12 achieving a > 50% reduction. TTV results showed partial response in 7/12, stable disease in 3/12, and progression in 2/12, correlating strongly with PSA trends. Salivary glands showed significantly lower post-TAT PSMA-PET SUV_max and SUV_mean (-63.7% and -45.5%, respectively). Moreover, elevated PSA, ALP, and LDH, along with low hemoglobin, platelet count, and creatinine, were associated with reduced overall survival (OS). Median progression-free survival (PFS) and OS were 27 and 53 weeks, respectively. The Barthel Index remained stable indicating preserved functional independence. These findings suggest that combining PSA, TTV, and blood biomarkers enhances the predictive accuracy and supports a more holistic evaluation of treatment efficacy. Validation in larger cohorts is warranted.

Compared to agonists, radiolabeled somatostatin receptor (SSTR) antagonists have advantages in neuroendocrine tumors (NETs). Articles on radiolabeled somatostatin receptor agonists or antagonists in NETs were included by searching the Web of Science (WoS) database. The included literature has been subjected to data collection and bibliometric study. A detailed analysis of the included clinical articles was also performed. 123 publications were identified for biblio-metric analysis. The number of publications on radiolabeled somatostatin receptor agonists and antagonists in the theranostics of NETs has increased significantly after 2014, with Germany publishing the most papers (39), followed by the United States (33) and Switzerland (28). The Swiss paper was cited the most, with 1783 quotations, followed by the USA (1338) and Germany (1330). The most common keywords were NETs (89), Peptide receptor-mediated radionuclide therapy (PRRT) (62), and antagonists (53). Antagonists had lower uptake in normal tissue and higher uptake in tumor tissue compared to agonists, with a high tumor-to-liver ratio. Research on radiolabeled somatostatin receptor agonists and antagonists in theranostics of NETs is increasing, with significant contributions from Europe and the United States. Radiolabeled somatostatin receptor antagonists are likely to be a hot topic in NETs theranostics.