Changes in regional brain perfusion during functional brain activation: Comparison of [64Cu]-PTSM with [14C]-Iodoantipyrine

A dilemma in behavioral brain mapping is that conventional techniques immobilize the subject, extinguishing all but the simplest behaviors. This is avoided if brain activation is imaged after completion of the behavior and tissue capture of the tracer. A single-pass flow tracer proposed for positron emission tomography (PET) is a radiolabeled copper(II) complex of pyruvaldehyde bis(N4-methylthiosemicarbazone), [Cu64]-PTSM. [Cu64]-PTSM reaches steady-state cerebral distribution more rapidly than the metabolic tracer [18F]-fluorodeoxyglucose, allowing imaging with substantially greater temporal resolution. Using dual-label autoradiography, this study compares the relative regional cerebral blood flow tracer distribution (CBF-TR) of [64Cu]-PTSM to that of the classic perfusion tracer [14C]-iodoantipyrine in a rat model during treadmill walking. Rats were exposed to continuous walking on a treadmill and compared to quiescent controls. [64Cu]-PTSM was bolus injected (iv) after 1 min, followed by a 5-minute uptake and subsequent bolus injection of [14C]-iodoantipyrine. CBF-TR was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping, as well as by region-of-interest analysis. A high homology was found between the [64Cu]-PTSM and [14C]-iodoantipyrine patterns of cerebral activation in cortical and subcortical regions. For white matter, however, [64Cu]-PTSM showed lower perfusion than [14Cu]-iodoantipyrine. [64Cu]-PTSM is a useful tracer for functional brain mapping in freely-moving subjects. Its application in conjunction with PET promises to increase our understanding of the neural circuitry of behaviors dependent on locomotion.