technetium-tc-99m-sulfur-colloid and HIV-Infections

Describing the distribution and clearance of HIV surrogates within the gastrointestinal tract to inform rectal microbicide development.. Radiolabeled simulated HIV-infected semen was administered, imaged, and biopsied to simulate and measure colonic HIV distribution after anal intercourse.. Healthy male subjects with a history of receptive anal intercourse and experience with the use of anal sex toys were recruited to this study. Apheresis isolated leukocytes were collected before simulated intercourse. These autologous leukocytes, radiolabeled with 9.25 MBq (111)Indium-oxine (cell-associated HIV surrogate), and sulfur colloid particles, labeled with 37 MBq (99m)Technectium (cell-free HIV surrogate), were mixed in 3 mL autologous seminal plasma. This simulated HIV-infected semen was administered to subjects via an artificial phallus with urethra after 5 minutes of simulated intercourse. Postdosing dual isotope Single photon emission computed tomography coupled with traditional computed tomography (SPECT/CT) images were acquired at 1, 4, 8, and 24 hours. At 5 hours postdosing, colon biopsies were collected, CD4 cells were extracted, and samples analyzed for radioactivity.. SPECT/CT images showed similar luminal distribution for both surrogates, with migration limited to the rectosigmoid colon in all subjects. SPECT showed at least 75% overlap in distribution of both surrogates up to 4 hours after dosing. Biopsies indicate that 2.4% of CD4 cells extracted from rectosigmoid colon tissue were exogenously administered.. Our HIV surrogates stayed within the rectosigmoid colon for 24 hours. Exogenously dosed autologous lymphocytes and HIV-sized particles migrate to similar locations and associate with the colonic tissue in the lumen.

Topics: Adult; Anti-Infective Agents; Colon; HIV Infections; Homosexuality, Male; Humans; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radioactive Tracers; Semen; Sexual Behavior; Technetium Tc 99m Sulfur Colloid; Time Factors; Tomography, X-Ray Computed

Rational development of drugs to prevent human immunodeficiency virus (HIV) transmission benefits from an understanding HIV distribution in the female genital tract after intercourse. This study describes HIV distribution using surrogates of cell-free and cell-associated HIV and semen.. Apheresis-derived, autologous, lymphocyte-rich cells radiolabeled with 3.7-MBq (100-μCi) indium 111 ((111)In)-oxine (cell-associated HIV surrogate) and 18.5-MBq (500-μCi) technetium 99m ((99m)Tc)-sulfur colloid (HIV-sized 100-nm particle, cell-free HIV surrogate) were resuspended in 3 mL of hydroxyethylcellulose gel (semen simulant) with gadoteridol and dosed via artificial phallus after simulated intercourse. Postdosing dual-isotope single photon emission computed tomography with computed tomography (SPECT/CT) and magnetic resonance (MR) images were acquired to determine the surrogates' distribution. Seven hours after dosing, vaginal biopsy and luminal samples were collected at discrete locations in 8 subjects.. SPECT/CT and MR analysis showed HIV and semen surrogate distribution with highest signal intensity in the vaginal pericervical area, without detectable signal in the uterus. One-third of the administered dose was retained in the female genital tract after 4 hours. Cell-free and cell-associated surrogate distribution coincided.. We demonstrate the feasibility of dual-isotope SPECT/CT and MR imaging to determine the distribution of HIV and semen surrogates after simulated intercourse without disrupting vaginal contents. Surrogate distribution suggests topical microbicides do not need to reach the uterus for efficacy.

Topics: Adult; Coitus; Female; HIV Infections; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Positron-Emission Tomography; Radioactive Tracers; Radiopharmaceuticals; Semen; Statistics, Nonparametric; Technetium Tc 99m Sulfur Colloid; Time Factors; Tomography, X-Ray Computed; Vagina; Young Adult

We sought to describe quantitatively the distribution of rectally administered gels and seminal fluid surrogates using novel concentration-distance parameters that could be repeated over time. These methods are needed to develop rationally rectal microbicides to target and prevent HIV infection.. Eight subjects were dosed rectally with radiolabelled and gadolinium-labelled gels to simulate microbicide gel and seminal fluid. Rectal doses were given with and without simulated receptive anal intercourse. Twenty-four hour distribution was assessed with indirect single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI), and direct assessment via sigmoidoscopic brushes. Concentration-distance curves were generated using an algorithm for fitting SPECT data in three dimensions. Three novel concentration-distance parameters were defined to describe quantitatively the distribution of radiolabels: maximal distance (D(max) ), distance at maximal concentration (D(Cmax) ) and mean residence distance (D(ave) ).. The SPECT/CT distribution of microbicide and semen surrogates was similar. Between 1 h and 24 h post dose, the surrogates migrated retrograde in all three parameters (relative to coccygeal level; geometric mean [95% confidence interval]): maximal distance (D(max) ), 10 cm (8.6-12) to 18 cm (13-26), distance at maximal concentration (D(Cmax) ), 3.8 cm (2.7-5.3) to 4.2 cm (2.8-6.3) and mean residence distance (D(ave) ), 4.3 cm (3.5-5.1) to 7.6 cm (5.3-11). Sigmoidoscopy and MRI correlated only roughly with SPECT/CT.. Rectal microbicide surrogates migrated retrograde during the 24 h following dosing. Spatial kinetic parameters estimated using three dimensional curve fitting of distribution data should prove useful for evaluating rectal formulations of drugs for HIV prevention and other indications.

Topics: Administration, Rectal; Adult; Anti-Infective Agents; Cellulose; Colon; Gadolinium; Gadolinium DTPA; Glycerol; HIV Infections; Homosexuality, Male; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Models, Theoretical; Pentetic Acid; Phosphates; Propylene Glycols; Semen; Sigmoidoscopy; Technetium Tc 99m Sulfur Colloid; Tomography, Emission-Computed, Single-Photon

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.

Topics: Administration, Rectal; Adult; Anti-HIV Agents; Anti-Infective Agents, Local; Cellulose; Coitus; Contrast Media; Diagnostic Imaging; Ejaculation; Enema; Feasibility Studies; Gadolinium DTPA; Gels; HIV Infections; Humans; Magnetic Resonance Imaging; Pilot Projects; Radiopharmaceuticals; Rectum; Semen; Sigmoidoscopy; Technetium Tc 99m Sulfur Colloid; Time Factors; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Unsafe Sex

The rate of seroconversion from percutaneous needlestick exposure to HIV infection is approximately 0.3 per cent. To investigate the possibility of local confinement of HIV, 100 to 200 nm Tc-99m sulfur colloid particles were injected in the canine model subcutaneously at the knee level and collected proximally at the groin from the cannulated femoral vein and lymphatic channel. Tourniquet compression (250 mm Hg) was used as an intervention to possibly restrict particle spread. It was found that particles arrived in the blood at 2.81 +/- 0.54 minutes, with later arrival in the lymph at 6.0 +/- 1.47 minutes. Tourniquet application delayed the appearance of the particulate matter in the blood up to 7.11 +/- 1.5 minutes and in lymph up to 40.0 +/- 5.10 minutes. The concentration of radioactivity in the lymph was higher than in the venous blood. The distribution of the particles reflected by flux was comparable in both pathways. The accumulation curves did not reach plateaus during 45 minutes in lymph and 15 minutes in blood. Radioactive scanning revealed that about 90 per cent of the injected particles remained locally with gradual release for at least 45 minutes. Our results suggest that HIV, introduced by needlestick injury, can be contained for possible viricidal treatment if the response includes rapid immobilization and tourniquet of the area.

Topics: Analysis of Variance; Animals; Dogs; HIV Infections; Humans; Lymph; Needlestick Injuries; Radionuclide Imaging; Technetium Tc 99m Sulfur Colloid; Tourniquets