SPECIES-DEPENDENT BINDING OF COPPER(II) BIS(THIOSEMICARBAZONE) RADIOPHARMACEUTICALS TO SERUM-ALBUMIN

Copper-62-labeled pyruvaldehyde bis(N-4-methylthiosemicarbazonato)-cop per(II) (Cu-PTSM) is a generator-based PET radiopharmaceutical under i nvestigation for use in evaluation of tissue perfusion. Despite promis ing results from animals, problems have been encountered in the use of Cu-62-PTSM to quantitate myocardial perfusion in humans at high flow rates, possibly due to species-dependent interactions of the tracer wi th serum albumin. Methods: Ultrafiltration and plasma/erythrocyte part itioning studies were performed to assess the protein binding of Cu-67 -labeled Cu-PTSM and six related copper(II) bis(thiosemicarbazone) com plexes. Results: These studies reveal significant interspecies variabi lity in the strength of Cu-PTSM binding to serum albumin, with (CU)-C- 67-PTSM binding much more strongly to human albumin than to dog albumi n. Most of the related Cu(II)bis(thiosemicarbazone) complexes examined exhibit interspecies variability of albumin binding similar to that o bserved with Cu-PTSM. Two such complexes, Cu-ETS and Cu-n-PrTS, howeve r, were identified that exhibit no preferential association with human serum albumin. Conclusion: Copper-62-PTSM exhibits substantial inters pecies variability in the strength of its binding to serum albumin, wh ich appears to explain the problems encountered in using animal data t o predict (CU)-C-62-PTSM behavior in humans. The Cu-62-ETS and (CU)-C- 62-n-PrTS complexes may be viable alternatives to Cu-62-PTSM for PET s tudies to evaluate quantitatively myocardial blood flow in humans.