Antiretroviral tissue kinetics: in vivo imaging using positron emission tomography.

摘要: Our current knowledge on the antiviral efficacy, dosing, and toxicity of available highly active antiretroviral therapy regimens is mostly derived from plasma or blood kinetics anti-human immunodeficiency virus (anti-HIV) drugs. However, comprises only 2% total target cells in body. Tissue drug levels may differ substantially corresponding levels, distribution processes be characterized by high intertissue variability, leading to suboptimal site concentrations potential risk for therapeutic failures. Positron emission tomography has greatly expanded scope pharmacokinetic measurements that can performed noninvasively animal models humans. We have prepared [18F]FPMPA, a fluorine-18-radiolabeled analogue tenofovir, study tissue vivo tested imaging probe rats. The biodistribution fluorine-18 closely follows nonfluorinated tenofovir. Compared blood, penetration were found significantly reduced spleen submandibular lymph nodes (approximately 2-fold), mesenteric testes 4-fold), brain compartment 25-fold). Intersubject variability trough concentration (measured at 120 min) certain tissues, like colon (coefficient variation, >100%), not reflected intersubject 24%). revealed accumulation cortex kidneys, correlate tenofovir-induced nephrotoxicity observed HIV-1-infected treated patients. Thus, [18F]FPMPA promising radiotracer evaluation tenofovir under carefully controlled administration protocols.