title: Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates.
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 (approximately 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.
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. chendrix@jhmi.edu
authors.forename: C W
authors.initials: CW
authors.lastname: Hendrix
authors.forename: E J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: K J
authors.initials: KJ
authors.lastname: Macura
authors.forename: L A
authors.initials: LA
authors.lastname: Lee
authors.forename: T L
authors.initials: TL
authors.lastname: Parsons
authors.forename: R P
authors.initials: RP
authors.lastname: Bakshi
authors.forename: W A
authors.initials: WA
authors.lastname: Khan
authors.forename: A
authors.initials: A
authors.lastname: Guidos
authors.forename: J P
authors.initials: JP
authors.lastname: Leal
authors.forename: R
authors.initials: R
authors.lastname: Wahl
mesh_terms: D000285:Administration, Rectal; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D002482:Cellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D003075:Coitus; D003287:Contrast Media; D003952:Diagnostic Imaging / Q000379:methods*; D004542:Ejaculation; D004733:Enema; D005240:Feasibility Studies; D019786:Gadolinium DTPA / Q000008:administration & dosage; D005782:Gels; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D008279:Magnetic Resonance Imaging; D010865:Pilot Projects; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D012007:Rectum / Q000378:metabolism* / Q000473:pathology; D012661:Semen / Q000378:metabolism; D012812:Sigmoidoscopy; D013671:Technetium Tc 99m Sulfur Colloid / Q000008:administration & dosage; D013997:Time Factors; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed; D047568:Unsafe Sex
chemical_list: D019380:Anti-HIV Agents; D000891:Anti-Infective Agents, Local; D003287:Contrast Media; D005782:Gels; D019275:Radiopharmaceuticals; D013671:Technetium Tc 99m Sulfur Colloid; D002482:Cellulose; C002283:hydroxyethylcellulose; D019786:Gadolinium DTPA