RT Journal Article
SR Electronic
T1 <strong>Synthesis and evaluation of a novel <sup>18</sup>F-labeled abirateron derivative</strong> <strong>for imaging CYP17A1 expression with positron emission tomography</strong>
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1135
OP 1135
VO 56
IS supplement 3
A1 Zhang, Zhengxing
A1 Jenni, Silvia
A1 Zhang, Chengcheng
A1 Pan, Jinhe
A1 Hundal-Jabal, Navjit
A1 Colpo, Nadine
A1 Benard, Francois
A1 Lin, Kuo-Shyan
YR 2015
UL http://jnm.snmjournals.org/content/56/supplement_3/1135.abstract
AB 1135 Objectives Intratumoral up-regulation of cytochrome P450 17A1 (CYP17A1), a key enzyme involved in androgen synthesis, is one of the main causes for the development of castration-resistant prostate cancer (CRPC). Suitable CYP17A1 targeting tracers could be used to select potential responders who could benefit from treatment with CYP17A1 inhibitors such as abiraterone. Herein, we present the synthesis and evaluation of a potent radiolabeled abiraterone derivative, 18F-(3β)​-17-​(4-​fluoro-​3-​pyridinyl)​-androsta-​5,​16-​dien-​3-​ol (18F-4’-FAbi; IC50 ≤ 11 nM) for imaging CYP17A1 expression with PET.Methods The radiolabeling precursor (3β)​-17-​(4-​chloro-​3-​pyridinyl)​-androsta-​5,​16-​dien-​3-​ol was synthesized in 4 steps from dehydroepiandrosterone. The 18F labeling was achieved via aromatic nucleophilic substitution using K[18F]F/K222 in DMF at 130 °C for 20 min, and 18F-4’-FAbi was purified by HPLC. PET/CT imaging and biodistribution studies were performed using male NODSCID/IL2RKO mice with CYP17A1-expressing testes serving as a surrogate of CYP17A1-expressing CRPC.Results 18F-4’-FAbi was obtained in 1.5 ± 0.6% decay-corrected radiochemical yield with &gt; 99% radiochemical purity. PET/CT imaging and biodistribution studies showed that 18F-4’-FAbi was cleared rapidly from blood, and excreted primarily via the hepatobiliary pathway. At 2 h post-injection (p.i.), only bone (12.1 ± 1.88 %ID/g), liver (3.36 ± 0.94 %ID/g), and intestines showed higher uptake than the CYP17A1-expressing testes (1.88 ± 0.17 %ID/g). The testes-to-blood and testes-to-muscle ratios at 2 h p.i. were 6.7 ± 1.3 and 6.7 ± 2.8, respectively.Conclusions 18F-4’-FAbi was successfully synthesized, and evaluated for imaging CYP17A1 expression in mice using testes as a surrogate target. Despite clear visualization of testes in PET images, 18F-4’-FAbi is not a suitable PET tracer due to its massive in vivo defluorination.