Pharmacokinetic Assessment of the Uptake of 16 beta-F-18-Fluoro-5 alpha-Dihydrotestosterone (FDHT) in Prostate Tumors as Measured by PET

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dc.contributor.authorBeattie, Bradley J.
dc.contributor.authorSmith-Jones, Peter M.
dc.contributor.authorJhanwar, Yuliya S.
dc.contributor.authorSchoeder, Heiko
dc.contributor.authorSchmidtlein, C. Ross
dc.contributor.authorMorris, Michael J.
dc.contributor.authorZanzonico, Pat
dc.contributor.authorSquire, Olivia
dc.contributor.authorMeirelles, Gustavo de Souza Portes [UNIFESP]
dc.contributor.authorFinn, Ron
dc.contributor.authorNamavari, Mohammad
dc.contributor.authorCai, Shangde
dc.contributor.authorScher, Howard I.
dc.contributor.authorLarson, Steven M.
dc.contributor.authorHumm, John L.
dc.contributor.institutionMem Sloan Kettering Canc Ctr
dc.contributor.institutionSt Lukes Roosevelt Hosp
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionStanford Univ
dc.date.accessioned2016-01-24T13:59:19Z
dc.date.available2016-01-24T13:59:19Z
dc.date.issued2010-02-10
dc.description.abstractThe aim of this study was to develop a clinically applicable non-invasive method to quantify changes in androgen receptor (AR) levels based on F-18-16 beta-fluoro-5 alpha-dihydrotestosterone (F-18-FDHT) PET in prostate cancer patients undergoing therapy. Methods: Thirteen patients underwent dynamic F-18-FDHT PET over a selected tumor. Concurrent venous blood samples were acquired for blood metabolite analysis. A second cohort of 25 patients injected with F-18-FDHT underwent dynamic PET of the heart. These data were used to generate a population-based input function, essential for pharmacokinetic modeling. Linear compartmental pharmacokinetic models of increasing complexity were tested on the tumor tissue data. Four suitable models were applied and compared using the Bayesian information criterion (BIC). Model 1 consisted of an instantaneously equilibrating space, followed by a unidirectional trap. Models 2a and 2b contained a reversible space between the instantaneously equilibrating space and the trap, into which metabolites were excluded (2a) or allowed (2b). Model 3 built on model 2b with the addition of a second reversible space preceding the unidirectional trap and from which metabolites were excluded. Results: the half-life of the F-18-FDHT in blood was between 6 and 7 min. As a consequence, the uptake of F-18-FDHT in prostate cancer lesions reached a plateau within 20 min as the blood-borne activity was consumed. Radiolabeled metabolites were shown not to bind to ARs in in vitro studies with CWR22 cells. Model 1 produced reasonable and robust fits for all datasets and was judged best by the BIC for 16 of 26 tumor scans. Models 2a, 2b, and 3 were judged best in 7, 2, and 1 cases, respectively. Conclusion: Our study explores the clinical potential of using F-18-FDHT PET to estimate free AR concentration. This process involved the estimation of a net uptake parameter such as the k(trap) of model 1 that could serve as a surrogate measure of AR expression in met-astatic prostate cancer. Our initial studies suggest that a simple body mass-normalized standardized uptake value correlates reasonably well to model-based k(trap) estimates, which we surmise may be proportional to AR expression. Validation studies to test this hypothesis are underway.en
dc.description.affiliationMem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA
dc.description.affiliationMem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA
dc.description.affiliationMem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA
dc.description.affiliationSt Lukes Roosevelt Hosp, Dept Radiol, New York, NY 10025 USA
dc.description.affiliationMem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA
dc.description.affiliationUniversidade Federal de São Paulo, Dept Radiol, São Paulo, Brazil
dc.description.affiliationStanford Univ, Dept Radiol & Bioengn, Bio X Program, Stanford, CA 94305 USA
dc.description.affiliationUnifespDepartment of Radiology, Federal University of Sao Paulo, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipMemorial Sloan-Kettering Center
dc.description.sponsorshipIDMemorial Sloan-Kettering Center: P50-CA92629
dc.description.sponsorshipIDMemorial Sloan-Kettering Center: P50 CA086438
dc.description.sponsorshipIDMemorial Sloan-Kettering Center: K23: CA102544
dc.format.extent183-192
dc.identifierhttp://dx.doi.org/10.2967/jnumed.109.066159
dc.identifier.citationJournal of Nuclear Medicine. Reston: Soc Nuclear Medicine Inc, v. 51, n. 2, p. 183-192, 2010.
dc.identifier.doi10.2967/jnumed.109.066159
dc.identifier.issn0161-5505
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32265
dc.identifier.wosWOS:000274152800018
dc.language.isoeng
dc.publisherSoc Nuclear Medicine Inc
dc.relation.ispartofJournal of Nuclear Medicine
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectmolecular imagingen
dc.subjectPET/CTen
dc.subjectradiotracer tissue kineticsen
dc.subjectFDHTen
dc.subjectdynamic PETen
dc.subjectpharmacokinetic modelingen
dc.subjectprostate canceren
dc.titlePharmacokinetic Assessment of the Uptake of 16 beta-F-18-Fluoro-5 alpha-Dihydrotestosterone (FDHT) in Prostate Tumors as Measured by PETen
dc.typeinfo:eu-repo/semantics/article
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