¹¹C-Acetate PET/CT in Localized Prostate Cancer: A Study with MRI and Histopathologic Correlation

Abstract

This work characterizes the uptake of 11C-Acetate in prostate cancer (PCa), benign prostate hyperplasia (BPH) and normal prostate tissue in comparison with multi-parametric MRI, whole mount histopathology and clinical markers, to evaluate its potential utility for delineating intra-prostatic tumors in a population of patients with localized PCa. METHODS 39 men with presumed localized PCa underwent dynamic/static abdomen-pelvic 11C-Acetate PET/CT for 30-minutes and 3T multi-parametric (MP) MRI prior to prostatectomy. PET/CT images were registered to MRI using pelvic bones for initial rotation-translation, followed by manual adjustments to account for prostate motion and deformation from the MRI endorectal coil. Whole-mount pathology specimens were sectioned using an MRI-based patient specific mold resulting in improved registration between the MRI, PET and pathology. 11C-Acetate PET standardized uptake values were compared with MP-MRI and pathology. RESULTS 11C-Acetate uptake was rapid but reversible, peaking at 3–5 minutes post-injection and reaching a relative plateau at ~10 minutes. The average SUVmax(10–12min) of tumors was significantly higher than that of normal prostate tissue (4.4±2.05, range 1.8–9.2 vs. 2.1±0.94, range 0.7–3.4; p<0.001); however it was not significantly different from benign prostatic hyperplasia (4.8±2.01; range 1.8–8.8). A sector-based comparison with histopathology, including all tumors > 0.5 cm, revealed a sensitivity and specificity of 61.6 % and 80.0 % for 11C-Acetate PET/CT, and 82.3% and 95.1% for MRI, respectively. Considering only tumors >0.9 cm the 11C-Acetate accuracy was comparable to that of MRI. In a small cohort (n=9), 11C-Acetate uptake was independent of fatty acid synthase expression based on immunohistochemistry. CONCLUSION 11C-Acetate PET/CT demonstrates higher uptake in tumor foci than normal prostate tissue; however 11C-Acetate uptake in tumors is similar to BPH nodules. While 11C-Acetate PET/CT is not likely to have utility as an independent modality for evaluation of localized PCa, the high uptake in tumors may make it useful for monitoring focal therapy, where tissue damage after therapy may limit anatomic imaging methods.

Organ-Specific Cancer Metabolism and Its Potential for Therapy

“…Although enzymes of mitochondrial β-oxidation are not increased in prostate cancer [140], it has been shown that etomoxir-mediated inhibition of mitochondrial β-oxidation at the level of carnitine palmitoyltransferase 1 induces cell death in prostate cancer cell lines [143]. Interestingly, prostate cancer also induces fatty acid biosynthesis by overexpressing fatty acid synthase early during tumor progression without lipid accumulation [144,145], which is further consistent with 11 C-acetate PET/CT experiments [146]. Why a futile cycle of simultaneous fatty acid oxidation and fatty acid synthesis is beneficial to prostate cancer cells remains an open question.…”

In Vivo Imaging of Prostate Cancer Using [68Ga]-Labeled Bombesin Analog BAY86-7548

“…11 C]-acetate PET/CT was only 62% (33). Similarly, MRI including magnetic resonance spectroscopy has been shown to outperform [ 11 C]-choline PET/CT in evaluation of primary disease (34) and multiple studies have shown low specificity of radiolabeled choline or acetate for prostate cancer imaging due to uptake in BPH (15,16,33).…”

Plasma Pharmacokinetics, Whole-Body Distribution, Metabolism, and Radiation Dosimetry of 68Ga Bombesin Antagonist BAY 86-7548 in Healthy Men

“…The most widely used tracer, 18 F-FDG, shows a high excretion in the urinary bladder and demonstrates generally an unsatisfactory uptake in PCa, especially in the early phase (4,5). Tracers that depict lipid metabolism such as 11 C-choline and 11 C-acetate have already been applied for imaging PCa, but they accumulate also in prostatic hyperplasia, with overlapping uptake in benign and malignant intraprostatic lesions (6)(7)(8). Consequently, there is an urgent need for more PCa-specific tracers.…”