Design and synthesis of a redox-active Tc-99m radiopharmaceutical with ferrocenedithiocarboxylate [FcCS = Fe(C5H4CS2)(C5H5)-].
The synthesis, at tracer level, of two Tc-99m complexes having the same chemical composition and structure, but differing by one electron in the total electron counting, is reported. These compounds have been prepared by reacting [99mTcO4]- with the piperidinium salt of the ligand ferrocenedithiocarboxylate {[Fe(II)(C5H4CS2)(C5H5)]- = FcCS}, in the presence of N-methyl S-methyldithiocarbazate as donor of N3-groups, and triphenylphosphine or SnCl2 as reducing agents. The formation of the neutral complex [99mTc(N)(FcCS)2] (compound A) and of the monocationic, mixed-valence complex [99mTc(N)(FcCS) (FcCS)]+ (compound B) {FcCS = [Fe(III)(C5H4CS2)(C5H5)]} was obtained in high yield. Both complexes comprise a terminal Tc triple bond N multiple bond and two FcCS ligands coordinated to the metal center through the two sulfur atoms of the -CS2 group, but they differ in the oxidation state of one of the two iron atoms of the coordinated FcCS ligands. In complex A, the two Fe atoms are both in the +2 oxidation state, while in B, one Fe atom is in the +2 and the other is in the +3 oxidation state. Thus, B is a mixed-valence Fe(II)-Fe(III) complex. B is easily converted into A by one-electron exchange with various reductants such as triphenylphosphine and excess SnCl2. Biodistribution studies in rats showed that complexes A and B are mostly retained in lungs and liver without any significant uptake in organs such as heart and brain.
Uccelli
L
L
Department of Clinical and Experimental Medicine, University of Ferrara, Italy.
Bolzati
C
C
Boschi
A
A
Duatti
A
A
Morin
C
C
Pasqualini
R
R
Giganti
M
M
Piffanelli
A
A
D000818:Animals; D005260:Female; D005296:Ferrous Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism; D010084:Oxidation-Reduction; D019275:Radiopharmaceuticals / Q000097:blood / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D005296:Ferrous Compounds; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C120320:technetium Tc 99m bis(ferrocenedithiocarboxylate)nitride