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First-in-Man Evaluation of 124I-PGN650: A PET Tracer for Detecting Phosphatidylserine as a Biomarker of the Solid Tumor Microenvironment
- Source :
- Molecular Imaging
- Publication Year :
- 2017
- Publisher :
- SAGE Publications, 2017.
-
Abstract
- Purpose: PGN650 is a F(ab′)2 antibody fragment that targets phosphatidylserine (PS), a marker normally absent that becomes exposed on tumor cells and tumor vasculature in response to oxidative stress and increases in response to therapy. PGN650 was labeled with 124I to create a positron emission tomography (PET) agent as an in vivo biomarker for tumor microenvironment and response to therapy. In this phase 0 study, we evaluated the pharmacokinetics, safety, radiation dosimetry, and tumor targeting of this tracer in a cohort of patients with cancer. Methods: Eleven patients with known solid tumors received approximately 140 MBq (3.8 mCi) 124I-PGN650 intravenously and underwent positron emission tomography–computed tomography (PET/CT) approximately 1 hour, 3 hours, and either 24 hours or 48 hours later to establish tracer kinetics for the purpose of calculating radiation dosimetry (from integration of the organ time-activity curves and OLINDA/EXM using the adult male and female models). Results: Known tumor foci demonstrated mildly increased uptake, with the highest activity at the latest imaging time. There were no unexpected adverse events. The liver was the organ receiving the highest radiation dose (0.77 mGy/MBq); the effective dose was 0.41 mSv/MBq. Conclusion: Although 124I-PGN650 is safe for human PET imaging, the tumor targeting with this agent in patients was less than previously observed in animal studies.
- Subjects :
- Male
Pathology
030218 nuclear medicine & medical imaging
Iodine Radioisotopes
chemistry.chemical_compound
0302 clinical medicine
Neoplasms
Positron Emission Tomography Computed Tomography
Tumor Microenvironment
Medicine
Tissue Distribution
Positron emission
human imaging
dosimetry
medicine.diagnostic_test
apoptosis
Phosphatidylserine
Middle Aged
Condensed Matter Physics
Positron emission tomography
030220 oncology & carcinogenesis
Molecular Medicine
Biomarker (medicine)
Female
Research Article
Biotechnology
Adult
medicine.medical_specialty
Biomedical Engineering
Phosphatidylserines
Young Adult
03 medical and health sciences
In vivo
Biomarkers, Tumor
cancer
Animals
Humans
Dosimetry
Radiology, Nuclear Medicine and imaging
Radiometry
Aged
Demography
Tumor microenvironment
business.industry
Cancer
Dose-Response Relationship, Radiation
medicine.disease
PET
chemistry
Positron-Emission Tomography
Radiopharmaceuticals
Tomography, X-Ray Computed
business
Nuclear medicine
Subjects
Details
- ISSN :
- 15360121
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- Molecular Imaging
- Accession number :
- edsair.doi.dedup.....a0a83b2659601faee7b3b3d519402233
- Full Text :
- https://doi.org/10.1177/1536012117733349