Fluoromisonidazole (
FMISO) has been shown to bind selectively to hypoxic cells in vitro and in vivo at radiobiologically significant
oxygen levels. When labeled with the positron emitter
fluorine-18 (F-18), its uptake in tissue can be detected quantitatively with high precision by positron emission transaxial tomography (
PETT). This paper presents the first experiences with
PETT imaging of [F-18]
FMISO uptake in human
malignancies, and describes the development of this technique as a tool for the non-invasive assessment of tumor hypoxia. Eight patients with selected
cancers were imaged prior to primary
radiotherapy, and 3 returned for follow-up scans, for a total of 11 imaging studies. Six of eight pre-
radiotherapy studies revealed retention of [F-18]
FMISO in
tumors that significantly exceeded plasma concentrations by 2 hr after
drug injection; all five patients with head and neck primaries had such "positive" scans. An analytic method for the interpretation of [F-18]
FMISO PETT images is presented, defining hypoxic elements within a
tumor volume as regions with a threshold regional
tumor:plasma [F-18]
FMISO ratio of greater than or equal to 1.4 by 2 or more hours after injection. Toward the end of a course of fractionated
radiotherapy, three repeat studies in patients with initially positive scans showed no
tumor accumulation of
drug above the threshold ratio of 1.4, suggesting reoxygenation had occurred. Pharmacokinetic and dosimetry data support continued use of [F-18]
FMISO as a safe
hypoxia probe. Two imaging protocols have been developed for human studies; a long protocol allows for more complete biodistribution and dosimetry information, and a shorter protocol facilitates increased patient accrual by applying a simple, clinically expedient imaging procedure. When correlated with
tumor outcome, [F-18]
FMISO PETT imaging may be developed as a predictor of
tumor response to conventional
radiotherapy. The implications of this technique in addressing persistent questions of tumor hypoxia in human oncology is discussed.