RESUMO
BACKGROUND: Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of 18F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated. METHODS: Eight patients were included and underwent 18F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUVmean) were determined as well as the corresponding area under the curve to compare 18F-MK-9470 uptake over time. Muscle uptake of 18F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue. RESULTS: 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with 18F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone. CONCLUSIONS: 18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton. Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.
RESUMO
BACKGROUND: Androgen deprivation (AD) is generally used as a first-line palliative treatment in prostate cancer (PCa) patients with rising prostate-specific antigen (PSA) after primary therapy. To acquire an accurate detection of tumour viability following AD with positron emission tomography (PET), an androgen-independent uptake of tracers would be advantageous. Several metabolic PET tracers are employed for detecting recurrent PCa. We evaluated the effect of AD on the uptake of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG), [11C]choline and [11C]acetate in vivo. METHODS: An [18F]FDG, [11C]choline and [11C]acetate baseline micro(µ)PET/µ computed tomography (CT) scan was subsequently performed in xenografts of androgen-sensitive (LAPC-4) and androgen-independent (22Rv1) tumours in nude mice. An untreated control group was compared to a surgical castration group, i.e. androgen-deprived group. µPET/µCT imaging with the above-mentioned tracers was repeated 5 days after the start of treatment. The percentage change of SUVmax and SUVmeanTH in the tumours was calculated. RESULTS: AD did not significantly affect the uptake of [18F]FDG and [11C]choline in LAPC-4 tumours as compared with the uptake of both tracers in untreated tumours. In control 22Rv1 tumours, [11C]choline and [18F]FDG uptake increased over time. However, compared with the uptake in control tumours, AD significantly decreased the uptake of [11C]choline and tended to decrease [18F]FDG uptake. [11C]acetate uptake remained unaffected by AD in both PCa xenograft models. CONCLUSIONS: [18F]FDG and especially [11C]choline PET, which is currently used for the detection of recurrent PCa, could miss or underestimate the presence of local recurrent PCa following AD therapy. [11C]acetate uptake occurs independently of androgens and thus may be more favourable for detecting tumour viability during or following AD.
RESUMO
PURPOSE: The aim of this study was to evaluate the impact of androgen ablation therapy in different prostate cancer (PCa) cell lines--reflecting different stages of the disease--on (18)F-fluorodeoxyglucose (FDG), 11C-choline and 11C-acetate uptake. METHODS: Uptake experiments were performed in androgen-sensitive (LNCaP, PC346C) and independent cell lines (22Rv1, PC346DCC, PC-3) as well as in a benign prostatic hyperplasia (BPH-1) cell line. Tracer uptake was assessed under androgen ablation. Results of the cancer cell lines were normalized to those of BPH-1. To evaluate the effect of androgen on the uptake of 18F-FDG, 11C-choline and 11C-acetate in PCa cell lines, 10(-8) M R1881, 10(-10) M R1881, the combination of 10(-10) M R1881 plus 10(-6) M Casodex or 10(-6) M Casodex alone were added in parallel cell cultures 1 day before uptake experiments. Uptake in androgen-supplemented cell cultures was compared to the uptake under androgen deprivation. Uptake was corrected for cell number using protein content. RESULTS: Compared to BPH-1, a higher 18F-FDG uptake was observed only in PC346C cells, whereas a higher 11C-choline and markedly increased 11C-acetate uptake was seen in all cancer cell lines. Androgens significantly modulated the uptake of 18F-FDG in LNCaP, PC346C and 22Rv1 cells, and of 11C-choline in the PC346C and 22Rv1 cell line. No androgenic effect on 11C-choline and 18F-FDG uptake was observed in PC-3 and PC346DCC cells. 11C-Acetate uptake was independent of androgen status in all PCa cell lines studied. CONCLUSION: 18F-FDG uptake in PCa cell lines showed the highest variability and strongest androgen effect, suggesting its poor potential for metabolic imaging of advanced PCa. In contrast to 18F-FDG and 11C-choline, 11C-acetate uptake was unaffected by androgens and thus 11C-acetate seems best for monitoring PCa progression.
