Quantitative imaging and sigmoidoscopy to assess distribution of rectal microbicide surrogates.
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.
Hendrix
C W
CW
Department of Medicine, Division of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA. chendrix@jhmi.edu
Fuchs
E J
EJ
Macura
K J
KJ
Lee
L A
LA
Parsons
T L
TL
Bakshi
R P
RP
Khan
W A
WA
Guidos
A
A
Leal
J P
JP
Wahl
R
R
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
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