Abstract
BackgroundHypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. We performed a clinical study to evaluate the safety, biodistribution, and imaging characteristics of 124I-IAZGP in patients with advanced colorectal cancer and head and neck cancer using serial positron emission tomography (PET) imaging.MethodsTen patients underwent serial whole-torso (head/neck to pelvis) PET imaging together with multiple whole-body counts and blood sampling. These data were used to generate absorbed dose estimates to normal tissues for 124I-IAZGP. Tumors were scored as either positive or negative for 124I-IAZGP uptake.ResultsThere were no clinical toxicities or adverse effects associated with 124I-IAZGP administration. Clearance from the whole body and blood was rapid, primarily via the urinary tract, with no focal uptake in any parenchymal organ. The tissues receiving the highest absorbed doses were the mucosal walls of the urinary bladder and the intestinal tract, in particular the lower large intestine. All 124I-IAZGP PET scans were interpreted as negative for tumor uptake.ConclusionsIt is safe to administer 124I-IAZGP to human subjects. However, there was insufficient tumor uptake to support a clinical role for 124I-IAZGP PET in colorectal cancer and head and neck cancer patients.Trial registrationClinicalTrials.gov NCT00588276
Highlights
Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models
Clinical study with 124I-IAZGP Under the auspices of a protocol approved by the Institutional Review Board and an Investigational New Drug application approved by the Food and Drug Administration (FDA), ten patients with either colorectal or head and neck cancer were intravenously administered 1 mg of IAZGP labeled with 124I after having provided informed consent
We found that the administration of 124IIAZGP was safe and that it was rapidly cleared from the body
Summary
Hypoxia within solid tumors confers radiation resistance and a poorer prognosis. 124I-iodoazomycin galactopyranoside (124I-IAZGP) has shown promise as a hypoxia radiotracer in animal models. The hypoxic tumor phenotype is complex; its various aspects include reduced sensitivity to low LET radiation, differential patterns of gene expression, enhanced angiogenesis, and an increased propensity to metastatic dissemination [1,2,3,4,5,6,7,8]. Positron emission tomography (PET) using hypoxiaselective radiotracers has been proposed as a non-invasive method of visualizing hypoxia within solid tumors. Typical candidate radiotracers for hypoxia imaging are radiolabeled small molecules that freely diffuse into (and out of) cells but are differentially metabolized in regions of low pO2. The molecules are irreversibly reduced and their radiolabeled metabolites bind to macromolecules, resulting in intracellular trapping. In non-hypoxic cells, the molecules remain operationally intact and diffuse back out again. Achieving a hypoxia imaging differential requires that the radiolabeled tracer accumulates in sufficient quantity in hypoxic regions while clearing relatively quickly from normoxic regions
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