Courtesy of Dr Gaurav Malviya, Prof Hing Leung and Dr David Lewis, this image shows longitudinal 18F-Fluciclovine PET/MRI imaging on the same mouse, either as a model of clinical androgen-dependent prostate cancer (bearing CWR22Res human prostate orthograft; top row) or castration-resistant prostate cancer (bearing 22Rv1 human prostate orthograft; bottom row). Imaging was performed to study tumour response following acute and chronic androgen deprivation therapy (ADT) in CWR22Res and 22Rv1 orthograft models, respectively. ADT remains the treatment of choice for incurable prostate cancer, however the majority of patients will show an initial favourable response to ADT but subsequently develop cancer recurrence (referred to as castration-resistant prostate cancer, CRPC). 18F-Fluciclovine uptakes highlight tumour heterogeneity that may explain castration resistance and can be exploited as a clinical biomarker.

To mimic clinical prostate cancer following acute ADT, mice bearing androgen-responsive CWR22Res orthografts were castrated, and PET/MRI scans were performed before and after ADT. As shown in the top row of the image above, analysis of PET data found a significant reduction in SUVmean values from the scan before ADT (a) to the scan after ADT (b), signifying a global reduction of tumoral 18F-Fluciclovine uptake following castration. However, the respective SUVpeak and SUVmax values before and after castration were comparable, and consequently tumour heterogeneity – as measured by the coefficient of variation across the tumour volume – was found to increase in acute ADT.

To mimic clinical prostate cancer following chronic ADT, castration-resistant 22Rv1 cells were orthotopically implanted and the mice castrated at the same time. Both scans were performed following ADT and, as shown in the bottom row of the image above, analysis of PET data found maintained SUVmean values between the two scans (c, d), albeit at relatively low levels. There was no significant change in the coefficient of variation across the tumour volume in chronic ADT.

These analyses support the concept that a tumour subpopulation with sustained 18F-Fluciclovine uptake following castration may represent cancer resistant to ADT and may therefore contribute to the development of CRPC. Findings from this study suggest that PET imaging following ADT may help clinicians to identify prostate cancer patients at high risk of early cancer recurrence and therefore provide the opportunity to consider additional treatment, while the bulk of resistant cancer remains low.

Overall, these findings are consistent with recent positive results from the FALCON study on the clinical impact of 18F-Fluciclovine PET imaging in management decisions in patients with recurrent prostate cancer.


The image is taken from a recent study published in EJNMMI Research:

Malviya, G, Patel, R, Salji, M, Martinez RS, Repiscak P, Mui E, Champion S, Mrowinska A, Johnson E, AlRasheedi M, Pimlott S, Lewis D, Leung HY. 18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy. EJNMMI Res 2020; 10:143.