title: The use of diaminodithiol for labeling small molecules with technetium-99m.
abstract: To investigate the labeling of small molecules with 99mTc by the bifunctional chelate approach, we have synthesized both a fatty acid and an estrone derivative containing a chelator of the N2S2 type. In the case of the fatty acid, this was a diaminodithiol (DADT) while for the estrone, a diaminodisulfide (DADS) was attached. The estrone derivative (5-(2-methylene estrone 3-methyl ether)-3,3,10,10-tetramethyl-1,2-dithia-5,8-diazacyclodecane hydrochloride, DADS-E) was prepared by alkylation of DADS while the fatty acid derivative (N-(11-undecanoic acid)-N,N'-bis(2-methyl-2-mercaptopropyl) ethylenediamine hydrochloride, DADT-FA) was synthesized by alkylation of DADS followed by reduction. DADS-E was labeled in ethanol at elevated temperatures while DADT-FA was labeled at room temperature, both by stannous reduction. Paper chromatography showed both to be labeled and reverse-phase HPLC showed multiple peaks for both. Serum stability studies were performed by incubation at 37 degrees C with aliquots removed at 1 min and 1 day for analysis by size-exclusion HPLC. Initially, little pertechnetate or binding to serum proteins was observed whereas after 1 day the majority of activity in both cases was protein bound with 20 and 38% pertechnetate appearing for DADT-FA and DADS-E respectively. In conclusion, small biologically active molecules may be labeled with 99mTc through an attached diaminodithiol or diaminodisulfide group.
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D002614:Chelating Agents; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis; D005029:Ethylenediamines / Q000097:blood / Q000138:chemical synthesis; D006801:Humans; D066298:In Vitro Techniques; D007553:Isotope Labeling; D011485:Protein Binding; D013667:Technetium / Q000097:blood
chemical_list: D001798:Blood Proteins; D002614:Chelating Agents; D005029:Ethylenediamines; C052631:N-(11-undecanoic acid)-N,N'-bis(2-methyl-2-mercaptopropyl)ethylenediamine; C052630:5-(2-methylene estrone 3-methyl ether)-3,3,10,10-tetramethyl-1,2-dithia-5,8-diazabicyclodecane; D004970:Estrone; D013667:Technetium