177Lu-AB-3PRGD2

177Lu-AB-3PRGD2 is a novel targeted radiopharmaceutical developed for the treatment of integrin αvβ3-positive tumors. It combines a PEGylated cyclic RGD dimer targeting integrin αvβ3 with an albumin-binding motif to optimize pharmacokinetics[1]. This compound represents an advancement in targeted radionuclide therapy (TRT), utilizing lutetium-177 (177Lu), which has a half-life of 6.7 days and relatively mild β-emission (Emax: 0.497 MeV)[3]. ## Development and Clinical Status The drug was initially developed by Peking Union Medical College Hospital in China[2]. It has reached early Phase 1 clinical trials, with studies evaluating its safety, pharmacokinetics, and dosimetry in patients with integrin αvβ3-avid tumors[1][2]. A first-in-human study investigated 177Lu-AB-3PRGD2 in 10 patients with advanced integrin αvβ3-avid tumors that were previously confirmed by 68Ga-DOTA-3PRGD2 PET/CT imaging[1]. The study found no remarkable acute adverse events during drug administration, and no life-threatening grade 4 or 5 toxicity was observed in any patients[1]. ## Mechanism of Action 177Lu-AB-3PRGD2 targets integrin αvβ3, which is highly expressed in some tumor cells and neovascularization, making it an ideal target for diagnosis and treatment of solid tumors[5][6]. The drug incorporates: 1. A PEGylated cyclic RGD dimer that specifically targets integrin αvβ3 2. An albumin-binding motif that optimizes pharmacokinetics and extends circulation time 3. Lutetium-177, which delivers therapeutic radiation to tumor sites[1] The albumin binder (AB) in the structure of 3PRGD2 was specifically introduced to achieve sustained antitumor effects[2]. ## Clinical Trials Several clinical trials are evaluating 177Lu-AB-3PRGD2: 1. An open-label, non-controlled, non-randomized study assessing safety and measuring image-based absorbed dose in patients with integrin αvβ3-positive tumors[6][8] 2. A study evaluating therapeutic efficacy in patients with various solid tumors, with treatment planned for up to 4 cycles at 6-week intervals using a fixed dose of 2.96 GBq (80 mCi)[5] 3. Patient selection typically involves whole-body 68Ga-RGD PET/CT scanning to confirm high RGD uptake in tumor lesions before 177Lu-AB-3PRGD2 administration[5][6] ## Safety Profile In the first-in-human study, adverse events were found in 3 out of 10 patients (30%)[1]: - One patient experienced grade 3 elevations of ALT and AST - Another patient showed grade 2 ALT elevation and grade 1 AST elevation - A third patient with borderline hemoglobin reported a grade 2 reduction All adverse events were manageable and most resolved within weeks[1]. 177Lu-AB-3PRGD2 represents a promising advancement in targeted radiopharmaceuticals for cancer treatment, particularly for tumors expressing integrin αvβ3.

Other names

Lutetium-177 AB-3PRGD2Lutetium177 AB-3PRGD2Lutetium 177 AB-3PRGD2177Lu-labeled AB-3PRGD2