Toxicology evaluation of radiotracer doses of 3-deoxy-3-18Ffluorothymidine 18F-FLT for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT dosesReportar como inadecuado




Toxicology evaluation of radiotracer doses of 3-deoxy-3-18Ffluorothymidine 18F-FLT for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

BMC Nuclear Medicine

, 7:3

First Online: 03 July 2007Received: 20 April 2007Accepted: 03 July 2007

Abstract

BackgroundF-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of F-FLT administered to human subjects, by: 1 performing an evaluation of the toxicity of F-FLT administered in radiotracer amounts for PET imaging, 2 comparing a radiotracer dose of FLT to clinical trial doses of FLT.

MethodsTwenty patients gave consent to a F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. F-FLT doses of 2.59 MBq-Kg with a maximal dose of 185 MBq 5 mCi were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours AUC12.

ResultsNo side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations p = 0.66. The blood samples-derived AUC12 values range from 0.232 ng*h-mL to 1.339 ng*h-mL with a mean of 0.802 ± 0.303 ng*h-mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h-mL reported by Flexner et al 1994. This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner-s twice daily trial.

ConclusionThis study shows no evidence of toxicity or complications attributable to F-FLT injected intravenously.

List of abbreviationsF-FLT3-deoxy-3- Ffluorothymidine

AUC12area under the curve for 12 hours

BUNblood urea nitrogen

NSCLCnon-small cell lung cancer

PETpositron emission tomography

RBCred blood cell count

TACtime-activity curve

TK-1thymidine kinase-1

WBCwhite blood cell count

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2385-7-3 contains supplementary material, which is available to authorized users.

Eric Turcotte contributed equally to this work.

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Autor: Eric Turcotte - Linda W Wiens - John R Grierson - Lanell M Peterson - Mark H Wener - Hubert Vesselle

Fuente: https://link.springer.com/







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