18F-RB390: innovative ligand for imaging the T877A androgen receptor mutant in prostate cancer via positron emission tomography (PET).

Bertolini, Reto; Göpfert, Christine; Andrieu, Thomas; Nichols, Sara; Walter, Martin Alexander; Frey, Felix J; McCammon, J Andrew; Frey, Brigitte (2015). 18F-RB390: innovative ligand for imaging the T877A androgen receptor mutant in prostate cancer via positron emission tomography (PET). Prostate, 75(4), pp. 348-359. Wiley-Blackwell 10.1002/pros.22919

[img] Text
pros22919.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (834kB) | Request a copy


Detecting prostate cancer before spreading or predicting a favorable therapy are challenging issues for impacting patient's survival. Presently, 2-[(18) F]-fluoro-2-deoxy-D-glucose ((18) F-FDG) and/or (18) F-fluorocholine ((18) F-FCH) are the generally used PET-tracers in oncology yet do not emphasize the T877A androgen receptor (AR) mutation being exclusively present in cancerous tissue and escaping androgen deprivation treatment.


We designed and synthesized fluorinated 5α-dihydrotestosterone (DHT) derivatives to target T877A-AR. We performed binding assays to select suitable candidates using COS-7 cells transfected with wild-type or T877A AR (WT-AR, T877A-AR) expressing plasmids and investigated cellular uptake of candidate (18) F-RB390. Stability, biodistribution analyses and PET-Imaging were assessed by injecting (18) F-RB390 (10MBq), with and without co-injection of an excess of unlabeled DHT in C4-2 and PC-3 tumor bearing male SCID mice (n = 12).


RB390 presented a higher relative binding affinity (RBA) (28.1%, IC50  = 32 nM) for T877A-AR than for WT-AR (1.7%, IC50  = 357 nM) related to DHT (RBA = 100%). A small fraction of (18) F-RB390 was metabolized when incubated with murine liver homogenate or human blood for 3 hr. The metabolite of RB390, 3-hydroxysteroid RB448, presented similar binding characteristics as RB390. (18) F-RB390 but not (18) F-FDG or (18) F-FCH accumulated 2.5× more in COS-7 cells transfected with pSG5AR-T877A than with control plasmid. Accumulation was reduced with an excess of DHT. PET/CT imaging and biodistribution studies revealed a significantly higher uptake of (18) F-RB390 in T877A mutation positive xenografts compared to PC-3 control tumors. This effect was blunted with DHT.


Given the differential binding capacity and the favorable radioactivity pattern, (18) F-RB390 represents the portrayal of the first imaging ligand with predictive potential for mutant T877A-AR in prostate cancer for guiding therapy. Prostate 75:348-359, 2015. © 2014 Wiley Periodicals, Inc.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie

UniBE Contributor:

Bertolini, Reto, Göpfert, Christine, Andrieu, Thomas, Walter, Martin Alexander, Frey, Brigitte


600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture








Barbara Gautschi-Steffen

Date Deposited:

30 Mar 2015 16:23

Last Modified:

05 Dec 2022 14:44

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

18F-DHT-derivative, PET-Imaging, PET/CT scan, T877A-androgen receptor mutant, androgen receptor, prostate cancer





Actions (login required)

Edit item Edit item
Provide Feedback