PHARMACOKINETIC ASSESSMENT OF NOVEL ANTICANCER DRUGS USING SPECTRAL-ANALYSIS AND POSITRON-EMISSION-TOMOGRAPHY - A FEASIBILITY STUDY

Purpose: The aim of this study was to investigate the feasibility of e valuating the pharmacokinetics of radiolabeled anti-cancer drugs using spectral analysis, a non-compartmental tracer kinetic modeling techni que, and positron emission tomography (PET). Methods: Dynamic PET stud ies were performed on patients receiving tracer doses of 5-fluorouraci l (5-[F-18]-FU) and two developmental drugs - [C-11]-temozolomide and [C-11]-acridine carboxamide. Spectral analysis was then used to (a) de termine individual and group average pharmacokinetics, (b) predict tum our handling in response to different drug administration regimens, an d (c) produce functional parametric images describing regional pharmac okinetics. Results: Spectral analysis could distinguish tumour kinetic s from normal tissue kinetics in an individual [C-11]-temozolomide stu dy and demonstrated a markedly greater volume of distribution (VD) in glioma than in normal brain, although there was no appreciable differe nce in mean residence time. Analysis of pooled acridine carboxamide da ta (n = 22) revealed a relatively large VD (and prolonged retention) i n the liver and spleen and a markedly lower VD (and initial uptake) in the brain. Continuous infusion of 5-[F-18]-FU was predicted to achiev e a concentration in colorectal metastases in liver approximately 10 t imes that achieved in plasma at 10 h after commencement of the infusio n. Conclusions: We conclude that spectral analysis provides important pharmacokinetic information about radiolabeled anti-cancer drugs with relatively few model assumptions.