Background:  Assessment of the distribution and clearance of microbicide gel after rectal administration is essential to the rational development of microbicides designed to outdistance and outlast a rectal HIV challenge. We have assessed the feasibility of measuring the anatomic dDistribution of a rectally applied microbicideal gel surrogate in the lower gastrointestinal tract using both direct endoscopic sampling and noninvasive dual SPECT/CT imaging.

Methods:  Three subjects received a single intra-rectal application of 10 mL of microbicide vehicle K-Y Jelly^R labeled with 500 µCi ^99mtechnetium (Tc)-sulphur colloid. After 4 hours supinesubjects has SPECT/CT imaging followed by sigmoidoscopicy sampling using cytology brushes. Beginning at a distance of 5 cm from the anal verge and advancing every 5 cm, separate brushes were used to sample for radiolabelled gel. Beginning 5cm beyond the anal sphincter at every 5cm interval up to 60cm, sepsrstr brushes were used to sample for radiolabelled gel. The absorbed radiolabelled gel in each brush (20 ml brush capacity) was measured in a gamma counter. ^99mTc distribution was compared between SPECT/CT and endoscopic methods.

Results:  Each subject demonstrated a unique SPECT/CT distribution of labeled gel. In all 3 subjects, there was no signal from the anus to the proximal rectal ampulla. The proximal rectosigmoid contained either 47%, 87%, or 99% of the total radioactivity based on region-of-interest measurements. For both subjects with less than 99% of the signal in the rectosigmoid, the remainder of the signal was distributed throughout the full length of the descending colon up to the splenic flexure, accounting for 53% and 13% of total dose, respectively. The endoscopic results were consistent with this overall pattern in that all 3 subjects had low levels of radioactivity detected in the distal rectum and ampulla (5cm to 10cm), which increased by 1 to 1.5 log₁₀ throughout the more proximal rectum and sigmoid colon (15cm to 35cm). In the 2 subjects with SPECT signal up to the splenic flexure, endoscopic sampling beyond 35 cm revealed radioactivity levels similar in magnitude to those in the rectosigmoid segments, with tapering at 60 cm. For the subject with minimal SPECT signal in the descending colon, the signal at 60cm was barely detectable.

Conclusions:  This study demonstrates the feasibility and comparability of measuring the distribution of radiolabeled gel using both SPECT/CT and direct endoscopic brush sampling. Strikingly, our microbicide surrogate gel vehicle dose reached to the splenic flexure in 2 out of 3 subjects based on both SPECT/CT and endoscopy measurements.

Keywords: Rectal Microbicides; Endoscopy; SPECT/CT