Faculty Bibliography

PURPOSE/OBJECTIVE:Neuroinflammation plays a critical role in various neuropathological conditions, and hence there is renewed interest in the translocator protein (TSPO) as a biomarker of microglial activation and macrophage infiltration in the brain. This is reflected in the large amount of research conducted seeking to replace the prototypical PET radiotracer (11)C-R-PK11195 with a TSPO ligand with higher performance. Here we report the in vivo preclinical investigation of the novel TSPO tracer (18)F-GE-180 in a rat model of stroke. METHODS:Focal cerebral ischaemia was induced in Wistar rats by 60-min occlusion of the middle cerebral artery (MCAO). Brain damage was assessed 24 h after MCAO by T2 MRI. Rats were scanned with (11)C-R-PK11195 and (18)F-GE-180 5 or 6 days after MCAO. Specificity of binding was confirmed by injection of unlabelled R-PK11195 or GE-180 20 min after injection of (18)F-GE-180. In vivo data were confirmed by ex vivo immunohistochemistry for microglial (CD11b) and astrocytic biomarkers (GFAP). RESULTS:(18)F-GE-180 uptake was 24 % higher in the core of the ischaemic lesion and 18 % lower in the contralateral healthy tissue than that of (11)C-R-PK11195 uptake (1.5 ± 0.2-fold higher signal to noise ratio). We confirmed this finding using the simplified reference tissue model (BPND = 3.5 ± 0.4 and 2.4 ± 0.5 for (18)F-GE-180 and (11)C-R-PK11195, respectively, with R 1 = 1). Injection of unlabelled R-PK11195 or GE-180 20 min after injection of (18)F-GE-180 significantly displaced (18)F-GE-180 (69 ± 5 % and 63 ± 4 %, respectively). Specificity of the binding was also confirmed by in vitro autoradiography, and the location and presence of activated microglia and infiltrated macrophages were confirmed by immunohistochemistry. CONCLUSION/CONCLUSIONS:The in vivo binding characteristics of (18)F-GE-180 demonstrate a better signal to noise ratio than (11)C-R-PK11195 due to both a better signal in the lesion and lower nonspecific binding in healthy tissue. These results provide evidence that (18)F-GE-180 is a strong candidate to replace (11)C-R-PK11195.

OBJECTIVE:To prospectively evaluate the effect of transrectal ultrasonography (TRUS)-guided prostate biopsy on erectile and voiding function at multiple time-points after biopsy. PATIENTS AND METHODS/METHODS:All men who underwent TRUS-guided prostate biopsy completed a five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptom Score (IPSS) before and at 1, 4 and 12 weeks after TRUS-guided biopsy. Statistical analyses used were a general descriptive analysis, continuous variables using a t-test and categorical data using chi-square analysis. A paired t-test was used to compare each patient's baseline score to their own follow-up survey scores. RESULTS:In all, 220 patients were enrolled with a mean age of 64.1 years and PSA level of 6.7 ng/dL. At initial presentation, 38.6% reported no erectile dysfunction (ED), 22.3% mild ED, 15.5% mild-to-moderate ED, 10% moderate ED, and 13.6% severe ED. On paired t-test there was a statistically significant reduction in IIEF-5 score at 1 week after biopsy compared with before biopsy (18.2 vs 15.5; P < 0.001). This remained significantly reduced at 4 (18.4 vs 17.3; P = 0.008) and 12 weeks (18.4 vs 16.9, P = 0.004) after biopsy. CONCLUSIONS:The effects of TRUS-guided prostate biopsy on erectile function have probably been underestimated. It is important to be aware of these transient effects so patients can be appropriately counselled. The exact cause of this effect is yet to be determined.