2025/10/15 by Chiyi Xiong, Boping Jing, Qizhen Cao +10
Biochemistry, Genetics and Molecular Biology · Medicine · #Metabolism, Diabetes, and Cancer #Epigenetics and DNA Methylation #Cancer-related Molecular Pathways
paper · doi:10.1021/acs.jmedchem.5c01760
Phenformin has antitumor effects against pancreatic cancer. We report a phenformin complex with the technetium-99m tricarbonyl [ 99m Tc(CO) 3 ], termed 99m Tc-Phen, that permitted noninvasive visualization of tumor uptake in models of pancreatic cancer by single-photon emission computed tomography. 99m Tc-Phen’s nonradioactive, structurally matched counterpart [Re(CO) 3 ]-phenformin, termed Re-Phen, showed antitumor activity against an orthotopic murine pancreatic ductal adenocarcinoma tumor with Kras G12D mutation in immunocompetent mice but not against orthotopically inoculated human MiaPaca-2 PDAC xenografts in nude mice. In vitro, Re-Phen was less potent than phenformin in inhibiting cell proliferation and colony formation and inducing cell death. However, Re-Phen but not phenformin potently reduced mitochondrial membrane potential. Unlike phenformin, Re-Phen caused no significant changes in mitochondrial ATP production or ATP generation by glycolysis at 10–100 μM, suggesting that Re-Phen and phenformin may act through distinct mechanisms. These findings underscore the potential utility of structurally matched Re/ 99m Tc(CO) 3 -biguanide complexes as a new class of theranostic pairs.