Successive positron emission tomography measurement of cerebral blood flow and neuroreceptors in the human brain: an 11C-SA4503 study

For evaluating a newly developed radioligand for positron emission tomography (PET), successive measurements of regional cerebral blood flow (rCBF) and the kinetics of the radioligand in the same subject are preferable in the first clinical trial. In this study, we demonstrate an example for the study of (11)C-labeled 1-(3,4-dimethoxyphenethyl)-4-(3-phenylprophyl) piperazine ((11)C-SA4503) for mapping sigma(1) receptors in the human brain. Five healthy male subjects underwent two successive PET scans with (15)O-H(2)O to measure the rCBF and with (11)C-SA4503 (dynamic 60-min scan). The brain kinetics of (11)C-SA4503 was evaluated using the time-activity curve (TAC) of tissue in each of the 11 regions of the brain and the metabolite-corrected TAC of plasma on the basis of a two-tissue compartment fourparameter model. The estimated parameters were four rate constants: K (1), influx from plasma to brain tissue; k (2), efflux from tissue to plasma; k (3), association between tracer and receptors; and k (4), dissociation of tracer-receptor complex, and the binding potential (BP), k (3)/k (4). (11)CSA4503 was distributed all over the brain, and the TACs exhibited an accumulation pattern in all the 11 regions. K (1) of (11)C-SA4503 correlated with rCBF, but the other three rate constant parameters and BP did not. The regional difference in the BP of (11)C-SA4503 is compatible with those of sigma(1) receptors. In conclusion, successive PET measurements of rCBF and the brain kinetics of radioligand-neuroreceptor binding are useful for the first clinical trial of a newly developed radioligand for mapping neuroreceptors, and the protocol is applicable to pathophysiological studies of brain disorders