177 Lu-NNS309

Investigational radiopharmaceutical compound vanc 6 July 2025 June 2026 177Lu-NNS309 177 Lu-NNS309.svg skin-invert-image Intravenous Radiation therapy Phase I clinical trials 6.7 days (177Lu component) [177Lu]Lu-NNS309 CCCCCC[C@H]1C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N2CCC[C@@H]2C(=O)NCC(=O)NCC(=O)N([C@H](C(=O)N[C@H](C(=O)N1)CC3=CC=C(C=C3)CNC(=O)COCCOCCNC(=O)CN4CCN(CCN(CCN(CC4)CC(=O)O)CC(=O)O)CC(=O)O)CC5=CC=CC=C5)C)CC(=O)O)CCCCNC(=O)N6CCN(CC6)CC(=O)O)CC7=CNC8=CC=CC=C87.[177Lu] InChI=1S/C89H128N20O25.Lu/c1-3-4-5-9-19-66-84(127)99-68(46-62-49-92-64-18-11-10-17-63(62)64)82(125)95-51-73(111)97-65(20-12-13-26-91-89(132)108-39-37-107(38-40-108)57-81(123)124)83(126)101-69(47-77(115)116)88(131)109-28-14-21-70(109)86(129)96-50-72(110)94-52-76(114)102(2)71(45-59-15-7-6-8-16-59)87(130)100-67(85(128)98-66)44-60-22-24-61(25-23-60)48-93-75(113)58-134-43-42-133-41-27-90-74(112)53-103-29-31-104(54-78(117)118)33-35-106(56-80(121)122)36-34-105(32-30-103)55-79(119)120;/h6-8,10-11,15-18,22-25,49,65-71,92H,3-5,9,12-14,19-21,26-48,50-58H2,1-2H3,(H,90,112)(H,91,132)(H,93,113)(H,94,110)(H,95,125)(H,96,129)(H,97,111)(H,98,128)(H,99,127)(H,100,130)(H,101,126)(H,115,116)(H,117,118)(H,119,120)(H,121,122)(H,123,124);/t65-,66-,67-,68-,69-,70+,71-;/m0./s1/i;1+2 NIMFRTFOYUYZQS-JXPRPOKFSA-N 177Lu-NNS309 is an investigational radiopharmaceutical compound currently under development by Novartis Pharmaceuticals for the treatment of various solid tumors. The compound is being evaluated in Phase I clinical trials for patients with pancreatic, lung, breast, and colorectal cancers. Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers NCT06562192 2025-07-11 https://clinicaltrials.gov/study/NCT06562192 Novartis Pharmaceuticals clinicaltrials.gov Chemical composition 177Lu-NNS309 is a radiopharmaceutical that combines the radioactive isotope lutetium-177 (177Lu) with the targeting compound NNS309. Lutetium-177 has been widely discussed as a radioisotope of choice for targeted radionuclide therapy, featuring simultaneous emission of imageable gamma photons [208 keV (11%) and 113 keV (6.4%)] along with particulate β− emission [β(max) = 497 keV], making it a theranostically desirable radioisotope. The radionuclide has a moderate beta energy similar to 131I and possesses a 6.7-day half-life. Dash A, Pillai MR, Knapp FF Production of (177)Lu for Targeted Radionuclide Therapy: Available Options Nuclear Medicine and Molecular Imaging 49 2 85–107 2015-06-01 26085854 4463871 10.1007/s13139-014-0315-z 1869-3474 Mechanism of action The therapeutic mechanism of 177Lu-NNS309 relies on targeted radionuclide therapy principles. NNS309 contains a nonapeptide that targets fibroblast activation protein, alpha (FAP-alpha). FAP is a transmembrane glycoprotein expressed on the surface of cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Giugliano F, Giordano E, Gilardi L, Salimbeni BT, Zagami P, Esposito A, Marra A, Trapani D, Berton Giachetti PP, Malagutti B, Henry T, Deandreis D, Curigliano G, Ceci F, Criscitiello C Radioligand Therapy in Metastatic Breast Cancer: Harnessing Precision Oncology Cancer Treatment Reviews 136 102940 May 2025 40228448 10.1016/j.ctrv.2025.102940 2434/1176179 free The nonapeptide is covalently linked to the metal chelating agent DOTA which binds 177Lu3+. The average path length of 177Lu particles in soft tissue is 670 μm, making this radionuclide ideal for delivering energy to small volumes, including micrometastatic disease, and tumor cells near the surface of cavities. 177Lu is a radioisotope that is increasingly explored as a therapeutic agent for treating various conditions, including neuroendocrine tumors and metastatic prostate cancer. Das T, Banerjee S Theranostic Applications of Lutetium-177 in Radionuclide Therapy Current Radiopharmaceuticals 9 1 94–101 2016 25771364 10.2174/1874471008666150313114644 1874-4729 Clinical development Phase I trials A Phase I open-label, multi-center study is currently evaluating the safety, tolerability, dosimetry, and preliminary activity of [177Lu]Lu-NNS309 in patients with pancreatic, lung, breast and colorectal cancers. The compound is being developed by Novartis Pharmaceuticals Corp. and has reached Phase 1 clinical trials status globally. Delving into the Latest Updates on [177Lu]Lu-NNS309 with Synapse https://synapse.patsnap.com/drug/9fef1c6649ec427a9119800e8419a2cf 2025-07-17 synapse.patsnap.com en Related compounds A diagnostic companion compound, [68Ga]Ga-NNS309, is also under development using gallium-68 instead of lutetium-177. This gallium-68 labeled version is being developed by Novartis Pharmaceuticals Corp. and has reached Phase 1 clinical trials for similar therapeutic areas including neoplasms, nervous system diseases, and various other conditions. Research https://med.stanford.edu/mosslab/research.html 2025-07-17 Moss Lab en-US Delving into the Latest Updates on [68Ga]Ga-NNS309 with Synapse https://synapse.patsnap.com/drug/c4d4133e5785466580e898f5e5849887 2025-07-17 synapse.patsnap.com en See also Lutetium-177 Radiopharmaceutical Theranostics References External links Novartis Clinical Trial Information IAEA 177Lu Development Project Category:Radiopharmaceuticals Category:Experimental cancer drugs Category:Lutetium complexes Category:Novartis Category:Targeted therapy