[68Ga]Ga DOTA-5G + [177Lu]Lu DOTA-ABM-5G

The drug "[68Ga]Ga DOTA-5G + [177Lu]Lu DOTA-ABM-5G" is a theranostic pair being investigated for the treatment of metastatic cancers. This combination consists of: * **Diagnostic component:** [68Ga]Ga DOTA-5G, using gallium-68 (positron-emitter, half-life 68 minutes) for PET/CT imaging. * **Therapeutic component:** [177Lu]Lu DOTA-ABM-5G, using lutetium-177 (beta-emitter, half-life 6.7 days) for targeted radiation therapy. Both components are peptide-based radiopharmaceuticals sharing the same targeting moiety, the 5G peptide (amino acid sequence GNGVPNLRGDLQVLGQRVGRT, with PEG moieties). The therapeutic component includes an albumin-binding moiety (ABM) to increase blood residence time and tumor uptake compared to formulations without ABM. The theranostic pair targets the integrin αvβ6, which is overexpressed in various malignancies. **Clinical Development:** It is currently in Phase 1 clinical trials for: * Metastatic carcinomas (NCT06389123) * Metastatic non-small cell lung cancer (NCT06228482) The first-in-human study showed that [68Ga]Ga DOTA-5G PET/CT can visualize disease for patient selection. The therapeutic component ([177Lu]Lu DOTA-ABM-5G) is being tested at dose levels up to 200 mCi. **Preclinical Data:** Preclinical studies indicate: * Binding to αvβ6-expressing cells (e.g., 9.7±1.0% binding to BxPC-3 cells). * Predominantly renal excretion. * Increased human serum albumin binding for [177Lu]Lu DOTA-ABM-5G (58.1±0.4%) vs. [177Lu]Lu DOTA-5G (16.2±0.4%). * High stability in human serum (≥97% intact at 24 hours). This approach offers a strategy for both detection and treatment of αvβ6-expressing metastatic carcinomas.