Iodine-123 metaiodobenzylguanidine (I-123 MIBG) is a crucial radiopharmaceutical widely used in nuclear medicine for its diagnostic capabilities in both cardiology and oncology. This review aims to present a comprehensive evaluation of the clinical applications of I-123 MIBG, focusing on its use in diagnosing and managing various diseases. In cardiology, I-123 MIBG has proven invaluable in assessing cardiac sympathetic innervation, particularly in patients with heart failure, where it provides prognostic information that guides treatment strategies. In oncology, I-123 MIBG is primarily utilized for imaging neuroendocrine tumors, such as neuroblastoma and pheochromocytoma, where it offers high specificity and sensitivity in the detection of adrenergic tissue. Additionally, its role in neurology, specifically in differentiating between Parkinson’s disease, dementia, and Lewy body dementia, has become increasingly significant due to its ability to identify postganglionic sympathetic dysfunction. Despite its established clinical utility, the use of I-123 MIBG is not without limitations, including variability in imaging protocols and interpretation challenges. This review will explore these issues and discuss emerging alternatives, while also highlighting areas where I-123 MIBG continues to be a gold standard. By synthesizing the current research, this article aims to provide a clear understanding of the strengths, limitations, and prospects of I-123 MIBG in clinical practice.

Prostate cancer is the second leading cause of cancer-related death in men, with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases representing a critical clinical challenge. Although radium-223 (Ra-223) is approved for treating mCRPC with bone metastases, its efficacy remains limited, necessitating the development of more effective therapies. This study investigates the therapeutic potential of ¹⁷⁷Lu-PSMA-617, a PSMA-targeted radiopharmaceutical, in a murine model of prostate cancer bone metastases. To our knowledge, this is the first study to systematically evaluate ¹⁷⁷Lu-PSMA-617 in an orthotopic bone metastatic prostate cancer model, providing a clinically relevant preclinical platform to assess both imaging and therapeutic performance. We conducted comprehensive preclinical evaluations, including synthesis, stability analysis, cell binding assays, nuclear imaging, in vivo biodistribution, pharmacokinetics, and antitumor efficacy. The synthesis of ¹⁷⁷Lu-PSMA-617 demonstrated high radiochemical yield (99.2%), molar activity (25.5 GBq/μmol), and purity (>98%), indicating high product quality. Stability studies confirmed minimal release of free Lutetium-177, maintaining the compound’s integrity under physiological conditions. In vitro assays showed selective binding and internalization in PSMA-positive LNCaP prostate cancer cells, with negligible uptake in PSMA-negative PC-3 cells. In vivo biodistribution studies demonstrated efficient tumor targeting, with peak uptake in LNCaP tumors (23.31 ± 0.94 %IA/g) at 4 h post-injection. The radiopharmaceutical exhibited favorable pharmacokinetics, with high tumor-to-background ratios (tumor-to-blood, 434.4; tumor-to-muscle, 857.4). Therapeutic efficacy was confirmed by significant survival extension in treated mice (30.7% for 37 MBq and 53.8% for 111 MBq), with median survival times of 34 and 40 days, respectively, compared to 26 days in the control group. Radiation dosimetry analysis indicated a favorable safety profile with a calculated effective dose of 0.127 mSv/MBq. These findings highlight the novelty and translational relevance of using ¹⁷⁷Lu-PSMA-617 in a clinically relevant bone metastasis model, reinforcing its potential as a dual-purpose agent for both targeted therapy and molecular imaging in advanced prostate cancer.

This work aimed to evaluate two albumin affinity structure-containing peptide-radionuclide conjugate drugs, INER-PP-F11N-1 and INER-PP-F11N-2, for the diagnosis/treatment of cholecystokinin receptor subtype 2 (CCK2R)-overexpressing cancers. We developed In-111- and Lu-177-labeled INER-PP-F11N radiopharmaceuticals and compared them with the current PP-F11N to investigate metabolic stability, biodistribution, SPECT/CT imaging, and therapeutic responses in CCK2R-expressing tumor xenograft mice. The metabolic stability of [¹¹¹In]In/[¹⁷⁷Lu]Lu-INER-PP-F11N remained above 90% for up to 144 h after labeling, indicating that the compound is highly stable under in vitro conditions. INER-PP-F11N showed 27% and 11% higher cellular uptake and internalization than PP-F11N, respectively. In vivo SPECT/CT imaging confirmed that INER-PP-F11N could accumulate at the tumor site of mice 24 h after receiving the two radiopharmaceutical agents. Biodistribution analysis revealed a significantly greater tumor uptake and reduced accumulation of INER-PP-F11N in the kidneys compared with PP-F11N. Furthermore, INER-PP-F11N significantly inhibited the growth of the CCK2R-overexpressing tumors in mice. The INER-PP-F11N radiopharmaceutical was superior as a theragnostic agent compared with the current PP-F11N. Our study suggests that INER-PP-F11N may be an innovative radiopharmaceutical agent for CCK2R-overexpressing tumors.

Hepatocellular carcinoma (HCC) remains one of the most common malignancies worldwide and a leading cause of cancer-related mortality. Current treatment options for advanced or unresectable HCC have limited efficacy and are often associated with systemic toxicity. In this study, a multifunctional, thermosensitive hydrogel-based delivery system was developed to enhance localized treatment of HCC. This system incorporates rhenium-188 sulfur colloid (¹⁸⁸Re-colloid), a β-emitting radiotherapeutic agent, and paclitaxel (PTX)-loaded micelles within a biodegradable PCL-PEG-PCL hydrogel matrix. The formulation enables in situ gelation at physiological temperatures, providing sustained release and prolonged retention of therapeutic agents at the tumor site. Physicochemical characterization confirmed the structural integrity and injectability of the formulations, while in vivo biodistribution studies in a murine hepatic tumor model demonstrated enhanced intratumoral accumulation and reduced systemic dispersion. The combined chemo-radiotherapeutic platform showed potential for improved therapeutic efficacy through synergistic action, offering a promising minimally invasive strategy for treating unresectable hepatocellular carcinoma.

Cholecystokinin B receptor (CCKBR) is a promising theranostic target because of its overexpression in several malignancies, including medullary thyroid carcinoma, small-cell lung cancer, gastric cancer, and pancreatic cancer. Its high-affinity ligand binding and efficient receptor-mediated internalization provide a strong biological basis for molecular imaging and peptide receptor radionuclide therapy (PRRT). Recent advances in radiolabeled gastrin and mini-gastrin analogues have improved tumor targeting, metabolic stability, and pharmacokinetic profiles, supporting their application in both diagnostic imaging and radionuclide therapy. This review summarizes the molecular biology and tumor expression of CCKBR, recent progress in SPECT/PET imaging and targeted radionuclide therapy, and advances in ligand and pharmacokinetic engineering. Despite substantial progress, CCKBR-targeted theranostics remain less clinically established than SSTR- or PSMA-based platforms. Major challenges include heterogeneous receptor expression, renal and gastric uptake, limited prospective clinical evidence, and the lack of standardized imaging, dosimetry, and treatment protocols. Addressing these limitations will be essential for the broader clinical translation of CCKBR-targeted theranostics.