Giron M C
Department of Pharmacology and Anesthesiology, University of Padua, Padua, Italy.
Q J Nucl Med Mol Imaging. 2009 Aug;53(4):359-64.
Since the advent of single photon emission computerized tomography (SPECT) and positron emission tomography (PET) various chemical ligands have been labeled with radionuclides and evaluated as tracer compounds in animal models to ascertain their suitability as potential radiopharmaceuticals for humans. In the absence of a defined algorithm to predict the diagnostic efficacy of a radiopharmaceutical, any new radioligand has to undergo preclinical evaluation even if it has excellent in vitro properties. Until now few studies have produced pharmacokinetic data that could be translated from animal models directly to humans. The purpose of this review is to highlight some critical aspects to consider during the development and validation phase of a new radiopharmaceutical. Interspecies differences and the absence of knowledge of physiological mechanism can become challenging drawbacks for obtaining a successful radiopharmaceutical. In this context, the influence of ABC transporters in neuroimaging, the effect of plasma protein binding and the consequence of anesthesia with reference to interspecies differences will be discussed with illustrative examples.
自从单光子发射计算机断层扫描（SPECT）和正电子发射断层扫描（PET）出现以来，各种化学配体已用放射性核素标记，并在动物模型中作为示踪化合物进行评估，以确定它们作为人类潜在放射性药物的适用性。在缺乏预测放射性药物诊断效果的明确算法的情况下，任何新的放射性配体都必须进行临床前评估，即使它具有优异的体外特性。到目前为止，很少有研究能够产生可直接从动物模型转化到人类的药代动力学数据。本综述的目的是强调在新放射性药物的开发和验证阶段需要考虑的一些关键方面。种间差异以及对生理机制缺乏了解可能成为获得成功放射性药物的具有挑战性的缺点。在这种情况下，将通过实例讨论ABC转运蛋白在神经成像中的影响、血浆蛋白结合的作用以及麻醉对种间差异的影响。
