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

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

Autor Beattie, Bradley J. Google Scholar
Smith-Jones, Peter M. Google Scholar
Jhanwar, Yuliya S. Google Scholar
Schoeder, Heiko Google Scholar
Schmidtlein, C. Ross Google Scholar
Morris, Michael J. Google Scholar
Zanzonico, Pat Google Scholar
Squire, Olivia Google Scholar
Meirelles, Gustavo de Souza Portes Autor UNIFESP Google Scholar
Finn, Ron Google Scholar
Namavari, Mohammad Google Scholar
Cai, Shangde Google Scholar
Scher, Howard I. Google Scholar
Larson, Steven M. Google Scholar
Humm, John L. Google Scholar
Instituição Mem Sloan Kettering Canc Ctr
St Lukes Roosevelt Hosp
Universidade Federal de São Paulo (UNIFESP)
Stanford Univ
Resumo The 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.
Palavra-chave molecular imaging
PET/CT
radiotracer tissue kinetics
FDHT
dynamic PET
pharmacokinetic modeling
prostate cancer
Idioma Inglês
Financiador Memorial Sloan-Kettering Center
Número do financiamento Memorial Sloan-Kettering Center: P50-CA92629
Memorial Sloan-Kettering Center: P50 CA086438
Memorial Sloan-Kettering Center: K23: CA102544
Data de publicação 2010-02-10
Publicado em Journal of Nuclear Medicine. Reston: Soc Nuclear Medicine Inc, v. 51, n. 2, p. 183-192, 2010.
ISSN 0161-5505 (Sherpa/Romeo, fator de impacto)
Publicador Soc Nuclear Medicine Inc
Extensão 183-192
Fonte http://dx.doi.org/10.2967/jnumed.109.066159
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000274152800018
Endereço permanente http://repositorio.unifesp.br/handle/11600/32265

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