Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates

C. W. Hendrix, E. J. Fuchs, K. J. MacUra, L. A. Lee, T. L. Parsons, R. P. Bakshi, W. A. Khan, A. Guidos, J. P. Leal, R. Wahl

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalClinical pharmacology and therapeutics
Volume83
Issue number1
DOIs
StatePublished - Jan 9 2008

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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