Technetium-99m N,N'-bis(2-mercapto-2-methylpropyl)-2-aminobenzylamine: technetium-99m complexes of a novel bis(aminoethanethiol) ligand.
A new N2S2 ligand system, N,N'-bis(2-mercapto-2-methylpropyl)-2- aminobenzylamine, U-BAT, 1, containing uneven amine groups (two amine groups with different pKa values) for complexing [TcVO]3+, was prepared. The reaction of this novel ligand with [99mTc]pertechnetate, in the presence of stannous tartrate as the reducing agent, produces the neutral and lipid-soluble [99mTc]TcVO(U-BAT), TcS2C15H23N2O, 2. However, when the same reaction was carried out at a higher pH, 9-10, and with 30 min of heating (100 degrees C), a second neutral but more lipid-soluble complex, [99mTc]TcVO(OU-BAT), TcS2C15H21N2O, 3, was isolated. The X-ray crystallography data of the 99Tc complexes show square pyramidal coordination with N2S2 as the base and the Tc = O in the apical position. Compound 3 can be derived from 2 by an oxidation of the ligand to form an imine. After iv injection into rats, the neutral and lipid-soluble technetium-99m complexes showed significant brain uptake, 1.54 and 1.07% dose/organ at 2 min for [99mTc]TcVO(U-BAT) and TcVO(OU-BAT), respectively. The novel Tc chemistry of this new ligand system may provide a useful foundation for designing Tc complexes with a built-in redox mechanism.
Francesconi
L C
LC
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Yang
Y Y
YY
Kung
M P
MP
Zhang
X X
XX
Billings
J J
JJ
Guo
Y Z
YZ
Kung
H F
HF
D000818:Animals; D001593:Benzyl Compounds; D001921:Brain / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013055:Spectrophotometry, Infrared; D017556:Technetium Compounds / Q000737:chemistry*; D014018:Tissue Distribution
D001593:Benzyl Compounds; D008024:Ligands; D015609:Organotechnetium Compounds; D017556:Technetium Compounds; C089708:technetium Tc 99m (oxo)(N,N'-bis(2-mercapto-2-methylpropyl)-2-aminobenzylimine); C089707:technetium Tc 99m oxo(N,N'-bis(2-mercapto-2-methylpropyl)-2-aminobenzylamine)