RELEASE OF CUPTSM FROM HUMAN SERUM-ALBUMIN AFTER ADDITION OF FATTY-ACIDS

Copper-62 labeled pyruvaldehyde bis (N-4-methyl-thiosemicarbazonato) c opper(II), CuPTSM, has been used to probe tissue perfusion by means of positron emission tomography. Despite promising results from animals, problems have been encountered in the use of (62)CuPTSM to quantitate regional myocardial blood flow in humans. Ultrafiltration and plasma/ erythrocyte partitioning studies with radiotracer have previously show n that CuPTSM is bound much more strongly by human serum albumin (HSA) than by dog serum albumin (DSA), limiting its ability to freely diffu se from blood into tissue. In this study, it is confirmed by electron spin resonance (ESR) that CuPTSM strongly binds to HSA with an apparen t g(parallel to) value of 2.12 and an apparent A(parallel to) value of 186 G. It is also shown that both spin-labeled stearic acid (5-SASL) and nonspin-labeled stearate inhibit CuPTSM binding to HSA. CuPTSM is completely released from HSA when the ratio of 5-SASL to HSA is 5:1. W hen pure sodium stearate is used, the binding of CuPTSM significantly decreased, about 73% of CuPTSM is released with a ratio of 4:1 stearat e to HSA. These results highlight a means of liberating CuPTSM from HS A.