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Metabolism of a [18F]fluorine labeled progestin (21 -[18F]fluoro-16α -ethyl-19-norprogesterone) in humans: a clue for future investigations
- Source :
- Nuclear Medicine and Biology. 21:941-952
- Publication Year :
- 1994
- Publisher :
- Elsevier BV, 1994.
-
Abstract
- Assessment of estrogen receptors and progesterone receptors (PR) with PET may allow the determination of the hormone responsiveness of tumors without the need for multiple biopsies, and the monitoring of the effect of hormonal therapy. In spite of the favourable characteristics of 21-[ 18 F]fluoro-16α-ethyl-19-norprogesterone ([ 18 F]FENP) found in preclinical studies, the compound failed to reveal the presence of PR in breast carcinomas and meningiomas. In view of the clinical significance of the PR assay in human breast cancer, it is worthwhile to explore mechanisms that are potentially involved in the inadequacy of [ 18 F]FENP to image PR with PET. Our present study on the in vivo metabolism of [ 18 F]FENP in humans demonstrates a rapid clearance and biotransformation of the compound. Results of incubation experiments suggest that the metabolic conversion of [ 18 F]FENP is not restricted to the liver, but also occurs in blood cells (presumably the erythrocytes) and tumors (breast carcinomas and meningiomas). The predominant metabolite of [ 18 F]FENP in plasma during the rapid distribution phase and in tumors is identified as 20-dihydro-[ 18 F]FENP. The conversion of [ 18 F]FENP to its 20α- or 20β-hydroxy metabolite has a deleterious effect on the binding affinity for PR. Our findings do not justify a conclusion as to the extent of in vivo extrahepatic biotransformation of [ 18 F]FENP, or its significance in the ineffectiveness of [ 18 F]FENP as an imaging agent for PR. On the other hand, the ability of breast carcinomas and meningiomas to metabolize [ 18 F]FENP avidly appears to preclude selective imaging of PR in these tumors during the time of a PET examination. It is imperative to evaluate the metabolic stability of a [ 18 F]fluorine labeled progestin in an early stage of future screening procedures.
- Subjects :
- Fluorine Radioisotopes
Cancer Research
medicine.medical_specialty
medicine.drug_class
Metabolite
Estrogen receptor
Breast Neoplasms
In Vitro Techniques
Biology
Gas Chromatography-Mass Spectrometry
Mice
chemistry.chemical_compound
In vivo
Internal medicine
medicine
Animals
Humans
Radiology, Nuclear Medicine and imaging
Receptor
Biotransformation
Screening procedures
Brain Neoplasms
Mammary Neoplasms, Experimental
Cancer
medicine.disease
Imaging agent
Endocrinology
Receptors, Estrogen
chemistry
Estrogen
Cancer research
Molecular Medicine
Meningioma
Receptors, Progesterone
Norprogesterones
Tomography, Emission-Computed
Subjects
Details
- ISSN :
- 09698051
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Nuclear Medicine and Biology
- Accession number :
- edsair.doi.dedup.....e8b09c3b4e7d48488138087d6c79ded4