11C-Acetate PET/CT in localized prostate cancer: a study with MRI and histopathologic correlation

Abstract

This work characterizes the uptake of (11)C-acetate in prostate cancer (PCa), benign prostate hyperplasia, and normal prostate tissue in comparison with multiparametric MRI, whole-mount histopathology, and clinical markers to evaluate the potential utility of (11)C-acetate for delineating intraprostatic tumors in a population of patients with localized PCa.

Methods: Thirty-nine men with presumed localized PCa underwent dynamic-static abdominal-pelvic (11)C-acetate PET/CT for 30 min and 3-T multiparametric MRI before prostatectomy. PET/CT images were registered to MR images 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. (11)C-acetate PET standardized uptake values were compared with multiparametric MRI and pathology.

Results: (11)C-acetate uptake was rapid but reversible, peaking at 3-5 min after injection and reaching a relative plateau at approximately 10 min. The average maximum standardized uptake value (10-12 min) 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], respectively; P < 0.001); however, it was not significantly different from that of benign prostatic hyperplasia (4.8 ± 2.01 [range, 1.8-8.8]). A sector-based comparison with histopathology, including all tumors greater than 0.5 cm, revealed a sensitivity and specificity of 61.6% and 80.0%, respectively, for (11)C-acetate PET/CT and 82.3% and 95.1%, respectively, for MRI. The (11)C-acetate accuracy was comparable to that of MRI when only tumors greater than 0.9 cm were considered. In a small cohort (n = 9), (11)C-acetate uptake was independent of fatty acid synthase expression using immunohistochemistry.

Conclusion: (11)C-acetate PET/CT demonstrates higher uptake in tumor foci than in normal prostate tissue; however, (11)C-acetate uptake in tumors is similar to that in benign prostate hyperplasia nodules. Although (11)C-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 when tissue damage after therapy may limit anatomic imaging methods.

Figures

Figure 1

Time activity-curve representing the mean of all patients, using iliac artery (red), prostate tumor (blue), benign prostatic hyperplasia (BPH) foci (purple) and normal prostate (green). Uptake is expressed in SUV (standardized uptake value). Tumor and BPH foci showed rapid uptake of 11C-Acetate in the prostate peaking ~3–5 minutes, followed by a relatively plateau after 10 minutes.

Figure 2

58-year-old male with prostate cancer. Axial T2-weighted MRI (A) demonstrates a low signal intensity focus in the right mid gland peripheral zone (white arrow), which shows 11C-Acetate uptake in the axial PET image (black arrow) (B). Fused 11C-Acetate PET/MRI (C) better localizes the tumor (black arrow). Corresponding pathology shows a Gleason 3+4 tumor in the right mid-peripheral zone (inked in black) (D).

Figure 3

69 year-old-male with prostate cancer. Axial T2-weighted MRI (A) and ADC map (B) show focal low signal intensity in the right mid-anterior central gland (white arrows), which demonstrates increased 11C-acetate uptake (black arrow) (C). Corresponding pathology (D) confirms the presence of tumor (Gleason 4+4), inked in green. Focal 11C-acetate uptake in the left central gland corresponds to a BPH nodule (red arrow) (C).

Figure 4

(A) Prostate tumors and benign prostatic hyperplasia (BPH) showed similar 11C-acetate uptake (p=0.757), while the SUV in normal prostate areas was significantly lower than tumor (p<0.0001). (B) No significant correlation was noted between SUV and serum PSA levels (r = 0.257) or (C) between 11C-Acetate uptake of lesions with lower Gleason scores (3+4 and below) and lesions with higher Gleason scores (4+3 and above), (p=0.064).

Figure 5

Immunohistochemical staining of fatty acid synthase in prostate cancers. Both 11C-acetate negative and positive cases were stained. Note the intense brown staining of most cells against the background stroma in most of the specimens, which can be recognized even at low power (A, C, E). Discrete differences in staining intensity were seen between benign tissue (arrowheads) and tumor (arrows); however no difference was seen between (A–D)11C-acetate-negative cases and (E–G)11C-acetate-positive cases. Negative controls showing no FAS staining (H). Magnification: (A, C, E)=5X; (B, D, F)=20X; G–H=10X.