Unknown

Dataset Information

0

Dosimetry of 18F-labeled tyrosine kinase inhibitor SKI-249380, a dasatinib-tracer for PET imaging.


ABSTRACT: PURPOSE:To obtain estimates of human normal-organ radiation doses of ¹?F-SKI-249380, as a prerequisite step towards first-in-human trial. ¹?F-SKI-249380 is a first-of-its-kind PET tracer for imaging the in vivo pharmacokinetics of dasatinib, an investigational targeted therapy for solid malignancies. PROCEDURES:Isoflurane-anesthetized mice received tracer dose via tail vein. Organ time-integrated activity coefficients, fractional urinary and hepatobiliary excretion, and total-body clearance kinetics were derived from PET data, with allometric extrapolation to the Standard Man anatomic model and normal-organ-absorbed dose calculations using OLINDA/EXM software. RESULTS:The human effective dose was 0.031 mSv/MBq. The critical organ was the upper large intestine, with a dose equivalent of 0.25 mSv/MBq. A 190-MBq administered activity of ¹?F-SKI-249380 is thus predicted to expose an adult human to radiation doses generally comparable to those of routinely used diagnostic radiopharmaceuticals. CONCLUSIONS:Animal-based human dose estimates support first-in-human testing of ¹?F-SKI-249380.

SUBMITTER: Dunphy MP 

PROVIDER: S-EPMC3113455 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Dosimetry of 18F-labeled tyrosine kinase inhibitor SKI-249380, a dasatinib-tracer for PET imaging.

Dunphy Mark P S MP   Zanzonico Pat P   Veach Darren D   Somwar Romel R   Pillarsetty Nagavarakishore N   Lewis Jason J   Larson Steven S  

Molecular imaging and biology 20120201 1


<h4>Purpose</h4>To obtain estimates of human normal-organ radiation doses of ¹⁸F-SKI-249380, as a prerequisite step towards first-in-human trial. ¹⁸F-SKI-249380 is a first-of-its-kind PET tracer for imaging the in vivo pharmacokinetics of dasatinib, an investigational targeted therapy for solid malignancies.<h4>Procedures</h4>Isoflurane-anesthetized mice received tracer dose via tail vein. Organ time-integrated activity coefficients, fractional urinary and hepatobiliary excretion, and total-body  ...[more]

Similar Datasets

| S-EPMC7248880 | biostudies-literature
| S-EPMC4918919 | biostudies-literature
| S-EPMC8348394 | biostudies-literature
| S-EPMC7142191 | biostudies-literature
| S-EPMC8524123 | biostudies-literature
| S-EPMC5556938 | biostudies-literature
| S-EPMC9291792 | biostudies-literature
| S-EPMC6015542 | biostudies-literature
| S-EPMC5817033 | biostudies-literature
| S-EPMC3121732 | biostudies-literature