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Biodistribution and Dosimetry of (18)F-EF5 in Cancer Patients With Preliminary Comparison of (18)F-EF5 Uptake Versus EF5 Binding in Human Glioblastoma

Cameron J Koch, Joshua S Scheuermann, Chaitanya Divgi, Kevin D Judy, Alexander V Kachur, Richard Freifelder, Janet S Reddin, Joel Karp, James B Stubbs, Stephen M Hahn, Jason Driesbaugh, Deborah Smith, Susan Prendergast, etc.

Eur J Nucl Med Mol Imaging. 2010 Nov;37(11):2048-59.

PMID: 20585774

Abstract:

Purpose:
The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of (18)F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of (18)F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies.
Methods:
(18)F-EF5 was synthesized by electrophilic addition of (18)F(2) gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC).
Results:
EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (∼3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ∼13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other (18)F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of (18)F-EF5 was confirmed by IHC.
Conclusion:
These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP152721374 EF5 EF5 152721-37-4 Price
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