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- Title
Quantitative Imaging and Sigmoidoscopy to Assess Distribution of Rectal Microbicide Surrogates.
- Authors
Hendrix, C. W.; Fuchs, E. J.; Macura, K. J.; Lee, L. A.; Parsons, T. L.; Bakshi, R. P.; Khan, W. A.; Guidos, A.; Leal, J. P.; Wahl, R.
- Abstract
Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29–102%; P<0.001), as far as the splenic flexure (∼60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.Clinical Pharmacology & Therapeutics (2008) 83, 97–105; doi:10.1038/sj.clpt.6100236; published online 16 May 2007
- Subjects
HIV; COLONOSCOPY; SPERMATOZOA; MEDICAL imaging systems; MAGNETIC resonance imaging; GASTROINTESTINAL system
- Publication
Clinical Pharmacology & Therapeutics, 2008, Vol 83, Issue 1, p97
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1038/sj.clpt.6100236