Radiolabeled-NeoB: A Dual-Action Diagnostic and Therapeutic Agent Targeting Gastrin-Releasing Peptide Receptors in...

Nuclear medicine has revolutionized diagnostic and therapeutic strategies in oncology by offering molecular-level insights into tissue function-often detecting pathological changes before they manifest structurally. At the heart of this advancement lies the growing field of radiotheranostics, which combines targeted molecular imaging with precision radiotherapy. One of the most promising molecular targets in this field is the Gastrin-Releasing Peptide Receptor (GRPR), which is overexpressed in several solid tumors, including prostate cancer, breast cancer, and Gastrointestinal Stromal Tumors (GISTs). Among the GRPR-targeting radiopharmaceuticals, NeoB (formerly NeoBOMB1)-a radiolabeled GRPR antagonist-has emerged as a potent agent, enabling both diagnostic imaging ([67/68Ga]Ga-NeoB) and targeted radionuclide therapy ([177Lu] Lu-NeoB). This narrative review examines the current state of NeoB-based radiopharmaceuticals in cancer, with a focus on their diagnostic and therapeutic applications, primarily in prostate cancer, breast cancer, and Gastrointestinal Stromal Tumors (GIST), including preclinical and clinical studies published up to January 2025. Additionally, limitations and future directions are addressed. In diagnostic imaging, [68Ga]Ga-NeoB PET/CT demonstrated high detection rates for primary tumors and distant metastases in GRPR-positive cancers, with moderate accuracy for detecting lymph node metastases. In therapeutic studies, [177Lu] Lu-NeoB showed strong tumor uptake and significant antitumor activity in preclinical models, with no observed toxicity. One ongoing multicenter clinical trial, initiated in 2019, is assessing the safety and efficacy of [177Lu] Lu-NeoB in patients with advanced or metastatic cancers, including those with moderate renal impairment. Despite encouraging findings, several limitations remain. GRPR is physiologically expressed in normal tissues such as the pancreas and kidneys, leading to non-specific uptake and potential off-target radiation. Optimizing molecular structure, radionuclide selection, and dosing strategies is essential to reduce toxicity. Moreover, long-term efficacy and safety data in humans are still lacking, and further largescale clinical trials are needed to validate NeoB's clinical utility.