A Pilot Study Measuring the Distribution and Permeability of a Vaginal HIV Microbicide Gel Vehicle Using Magnetic Resonance Imaging, Single Photon Emission Computed Tomography/Computed Tomography, and a Radiolabeled Small Molecule

Edward J. Fuchs, Jill L. Schwartz, David R. Friend, Jenell S. Coleman, Craig W. Hendrix

Research output: Contribution to journalArticle

Abstract

Vaginal microbicide gels containing tenofovir have proven effective in HIV prevention, offering the advantage of reduced systemic toxicity. We studied the vaginal distribution and effect on mucosal permeability of a gel vehicle. Six premenopausal women were enrolled. In Phase 1, a spreading gel containing 99mtechnetium-DTPA (99mTc) radiolabel and gadolinium contrast for magnetic resonance imaging (MRI) was dosed intravaginally. MRI was obtained at 0.5, 4, and 24 h, and single photon emission computed tomography with conventional computed tomography (SPECT/CT) at 1.5, 5, and 25 h postdosing. Pads and tissues were measured for activity to determine gel loss. In Phase 2, nonoxynol-9 (N-9), containing 99mTc-DTPA, was dosed as a permeability control; permeability was measured in blood and urine for both phases. SPECT/CT showed the distribution of spreading gel throughout the vagina with the highest concentration of radiosignal in the fornices and ectocervix; signal intensity diminished over 25 h. MRI showed the greatest signal accumulation in the fornices, most notably 1-4 h postdosing. The median (interquartile range) isotope signal loss from the vagina through 6 h was 29.1% (15.8-39.9%). Mucosal permeability to 99mTc-DTPA following spreading gel was negligible, in contrast to N-9, with detectable radiosignal in plasma, peaking at 8 h (5-12). Following spreading gel dosing, 0.004% (0.001-2.04%) of the radiosignal accumulated in urine over 12 h compared to 8.31% (7.07-11.01%) with N-9, (p=0.043). Spreading gel distributed variably throughout the vagina, persisting for 24 h, with signal concentrating in the fornices and ectocervix. The spreading gel had no significant effect on vaginal mucosal permeability.

Original languageEnglish (US)
Pages (from-to)1109-1115
Number of pages7
JournalAIDS research and human retroviruses
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'A Pilot Study Measuring the Distribution and Permeability of a Vaginal HIV Microbicide Gel Vehicle Using Magnetic Resonance Imaging, Single Photon Emission Computed Tomography/Computed Tomography, and a Radiolabeled Small Molecule'. Together they form a unique fingerprint.

  • Cite this