Biodistribution and dosimetry of (18)F-EF5 in cancer patients with preliminary comparison of (18)F-EF5 uptake versus EF5 binding in human glioblastoma.
OBJECTIVE
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.


CONCLUSIONS
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.
Koch
Cameron J
CJ
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. kochc@mail.med.upenn.edu
Scheuermann
Joshua S
JS
Divgi
Chaitanya
C
Judy
Kevin D
KD
Kachur
Alexander V
AV
Freifelder
Richard
R
Reddin
Janet S
JS
Karp
Joel
J
Stubbs
James B
JB
Hahn
Stephen M
SM
Driesbaugh
Jason
J
Smith
Deborah
D
Prendergast
Susan
S
Evans
Sydney M
SM
D001692:Biological Transport; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia; D017341:Etanidazole / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism* / Q000493:pharmacokinetics*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011874:Radiometry; D014018:Tissue Distribution; D051598:Whole Body Imaging; D005466:Fluorocarbons
D017341:Etanidazole; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons