title: Uptake of cationic technetium complexes in cultured human carcinoma cells and human xenografts.
abstract: We evaluated lipophilicity, in vitro cell accumulation, and biodistribution of a series of 99mTc-ether isonitrile complexes to determine whether increased lipophilicity promotes extraction by tumor or enhances imaging properties of the radiopharmaceutical. Nine 99mTc-sestamibi analogs were synthesized and their lipophilicity was determined. Net cellular accumulation and membrane-potential-independent uptake were quantitatively compared in cultured human colon, breast, and lung carcinoma cells. The biodistribution of [99mTc-(2-methoxy-2-ethyl-isocyanopropane)6]+ (99mTc-MMBI) and [99mTc-(2-ethoxy-2-methyl-1-isocyanopropane)6]+ (99mTc-EIBI) was studied in nude mice using subcutaneous, subrenal capsule, and hepatic tumor xenografts. Accumulation of these compounds in colon cells correlated with increasing lipophilicity. Compared with 99mTc-sestamibi, 99mTc-EIBI exhibited (i) in colon cells both higher net accumulation and a higher specific/nonspecific uptake ratio; (ii) in all three cell lines higher membrane-potential-dependent accumulation; and (iii) in all subcutaneous tumor xenografts and in colon subrenal capsule and hepatic tumor xenografts higher tumor/background ratios.
authors.affiliation: Department of Radiology, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA. barbaric@warren.med.harvard.edu
authors.forename: E
authors.initials: E
authors.lastname: Barbarics
authors.forename: J F
authors.initials: JF
authors.lastname: Kronauge
authors.forename: A
authors.initials: A
authors.lastname: Davison
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry*; D002412:Cations / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000737:chemistry*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009570:Nitriles / Q000737:chemistry; D013370:Subrenal Capsule Assay; D017556:Technetium Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D017256:Technetium Tc 99m Sestamibi / Q000031:analogs & derivatives / Q000737:chemistry; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D002412:Cations; D009570:Nitriles; D017556:Technetium Compounds; D017256:Technetium Tc 99m Sestamibi