Release of CuPTSM from human serum albumin after addition of fatty acids.
Copper-62 labeled pyruvaldehyde bis (N4-methyl-thiosemicarbazonato) copper(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 62CuPTSM to quantitate regional myocardial blood flow in humans. Ultrafiltration and plasma/erythrocyte partitioning studies with radiotracer have previously shown that CuPTSM is bound much more strongly by human serum albumin (HSA) than by dog serum albumin (DSA), limiting its ability to freely diffuse from blood into tissue. In this study, it is confirmed by electron spin resonance (ESR) that CuPTSM strongly binds to HSA with an apparent gparallel value of 2.12 and an apparent Aparallel 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. When pure sodium stearate is used, the binding of CuPTSM significantly decreased, about 73% of CuPTSM is released with a ratio of 4:1 stearate to HSA. These results highlight a means of liberating CuPTSM from HSA.
Yuan
H
H
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226, USA.
Antholine
W E
WE
Subczynski
W K
WK
Green
M A
MA
D004578:Electron Spin Resonance Spectroscopy; D005227:Fatty Acids / Q000737:chemistry*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry*
D005227:Fatty Acids; D009942:Organometallic Compounds; D012709:Serum Albumin; D013882:Thiosemicarbazones; C052629:copper pyruvaldehyde bis(N(4)-methylthiosemicarbazone) complex