Synthesis and evaluation of copper radiopharmaceuticals with mixed bis(thiosemicarbazone) ligands

Citation
Lj. Ackerman et al., Synthesis and evaluation of copper radiopharmaceuticals with mixed bis(thiosemicarbazone) ligands, NUCL MED BI, 26(5), 1999, pp. 551-554
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research Diagnosis & Treatment
Journal title
NUCLEAR MEDICINE AND BIOLOGY
ISSN journal
0969-8051 → ACNP
Volume
26
Issue
5
Year of publication
1999
Pages
551 - 554
Database
ISI
SICI code
0969-8051(199907)26:5<551:SAEOCR>2.0.ZU;2-C
Abstract
Four "mixed" bis(thiosemicarbazone) derivatives of pyruvaldehyde were synth esized that incorporate two dissimilar thiosemicarbazone functions. The cor responding [Cu-67]copper(II) complexes were prepared and evaluated as possi ble copper radiopharmaceuticals. The pyruvaldehyde-based mixed bis(thiosemi carbazone) ligands, CH3C[=NNHC(S)NHMe]CH[=NNHC(S)NHEt] (1), CH3C[=NNHC(S)NH Me]CH[=NNHC(S)NEt2] (2), CH3C[=NNHC(S)NHMe]CH[=NNHC(S)-cyclo-N(CH2)(5)] (3) , and CH3C [=NNHC(S)NHMe]CH[=NNHC(S)-cyclo-N(CH2)(6)] (4), were obtained by reaction of the appropriate thiosemicarbazide derivative with pyruvaldehyd e-2-N-4-methylthiosemicarbazone (CH3C[=NNHC(S) NHMe]CHO). The Cu-67-labeled copper(II) complexes of ligands 1-4 were prepared and screened in a rat mo del to assess the potential of each chelate as a Cu-62-radiopharmaceutical for imaging with positron emission tomography. The Cu-67-complexes of ligan ds 1-4 exhibit significant uptake into the brain and heart 1 min following intravenous administration to rats. For the Cu-67-complexes of ligands 2, 3 , and 4, the cerebral and myocardial uptake of Cu-67 is two-to-threefold lo wer at 2 h than at 1 min postinjection, due to significant biological clear ance of these Cu-67-chelates. However, the Cu-67-complex of 1 affords cereb ral and myocardial uptake and retention comparable to that of [Cu-67]Cu-PTS M in this model. Although the kinetics of this new agent appear attractive, ultrafiltration studies using solutions of dog and human serum albumin rev eal that the Cu-67-complex of ligand 1, like Cu-PTSM, interacts more strong ly with human albumin than dog albumin. Thus, this new agent would appear t o offer no advantage over Cu-PTSM as a Cu-62-labeled tracer for evaluation of regional tissue perfusion. (C) 1999 Elsevier Science Inc. All rights res erved.