‘3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma

• Verfasst von: Friebe, Matthias [VerfasserIn]
• Verfasst von: Eisenhut, Michael [VerfasserIn]
• Titel: ‘3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma
• Titelzusatz: synthesis and evaluation in vitro and in vivo
• Verf.angabe: Matthias Friebe, Ashfaq Mahmood, Hartmut Spies, Ralf Berger, Bernd Johannsen, Ashour Mohammed, Michael Eisenhut, Cristina Bolzati, Alan Davison, and Alun G. Jones
• E-Jahr: 2000
• Jahr: June 21, 2000
• Umfang: 8 S.
• Fussnoten: Gesehen am 09.02.2021
• Titel Quelle: Enthalten in: Journal of medicinal chemistry
• Ort Quelle: Washington, DC : ACS, 1959
• Jahr Quelle: 2000
• Band/Heft Quelle: 43(2000), 14, Seite 2745-2752
• ISSN Quelle: 1520-4804
• DOI: doi:10.1021/jm000050e
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1747876720

Abstract

‘3+1' Mixed-ligand [99mTc]oxotechnetium complexes with affinity for melanoma were synthesized in a one-pot reaction. Complexation of technetium-99m with a mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et2N(CH2)2] and N-(2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn2+ as the reducing agent resulted in the formation of ‘3+1' mixed-ligand technetium-99m complexes [TcO(SN(R)S)(SNX2)] in high radiochemical yield (60−98%). In vitro uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%) of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of compounds 1−6 in the C57Bl6/B16 mouse melanoma model demonstrated tumor localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at 60 min after injection. In vivo, 2 also showed a low blood-pool activity and high melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results suggest that small technetium-99m complexes could be useful as potential melanoma-imaging agents.