Effects of hormonal therapy on [18F]FDG and [11C]choline in vitro uptake on several prostatic cell lines

Introduction: Androgens influence prostate cancer (PC) cell growth by acting on cell cycle and hormones ablation is the first line of therapeutic intervention until the tumour became hormone refractory. Anti-androgen therapy is based on the blockade of ARs (Androgen Receptors) through the administration of AR[1] antagonist or the reduction of androgen levels through the activation of GnRH receptors[2]. [11C]Choline-PET imaging is extensively used in clinical practice for patients restaging following an increase in PSA levels[3]. However, androgen effects on tracer uptake has been poorly investigated. We studied the effect of the androgen Dihidrotestosterone (DHT), Triptorelin (GnRH agonist), Bicalutamide (AR antagonist) on [11C]Choline and [18F]FDG uptake on two different PC cell lines: human androgen sensitive LNCaP cells and androgen independent, AR positive murine cells TRAMP-C1. Methods: PC cells were divided in several groups of treatment as follows: a) DHT 10-9M, Triptorelin 10–7M alone or in combination with DHT 10-9M and a control group; b) DHT 10-9M, Bicalutamide 10-4 or 10-5M alone or in combination with DHT 10-9M and a control group. Cells were incubated with [18F]FDG (1µCi/ml) for 60 min or with [11C]Choline (4µCi/ml) for 30 min. Radiotracers uptake was expressed as % Uptake= (radioactivity in the cells/total radioactivity added) x 100 and normalized to total protein content. In parallel a MTS assay was performed to evaluate the toxicity of treatments. Results: DHT increased [18F]FDG and [11C]Choline uptake in LNCaP and TRAMP-C1 cells. In addition it increased cell growth in LNCaP cells as showed by MTS assay. Triptorelin increased [18F]FDG uptake only in LNCaP. Treatment with Bicalutamide had not effect on radiotracers uptake in LNCaP cells, whereas in doses of 10-4M it significantly inhibited cell growth, effect that was not inhibited by DHT co-treatment. In TRAMP-C1 cells Bicalutamide particularly in dose of 10-4M increased [18F]FDG uptake. As observed in LNCaP cells, Bicalutamide 10-4M inhibited significantly cell growth in TRAMP-C1 cells. Conclusions: As expected radiotracers uptake was modulated by DHT in both cell lines. Contrary to what expected, treatment with the AR antagonist Bicalutamide didn’t modulate tracers uptake in androgen sensitive cells (LNCaP), whereas it increased [18F]FDG uptake in androgen-independent AR positive cells (TRAMP-C1) although reducing cell growth. Finally Triptorelin treatment increased [18F]FDG uptake in LNCaP, but not in TRAMP-C1. Results of our study indicated that radiotracers uptake is influenced by AR receptors as indicated by DHT effects. These effects were not inhibited by the administration of the AR antagonist Bicalutamide that when it was administered alone, surprisingly increased the relative uptake of [18F]FDG in residual cells. Finally Triptorelin effect observed in LNCaP but not in TRAMP-C1 may be due to different expression or function of GnRH in the two types of PC cell lines. References: [1] Gelman EP; J Clin Oncl 20:3001-15 (2002) [2] Dondi D et al; Cancer Res 54:4091-4095 (1994) [3] Algan O et al; Radiat Res 146(3):267-75 (1996)