Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy–treated macaques

Abstract

The detection of viral dynamics and localization in the context of controlled HIV infection remains a challenge and is limited to blood and biopsies. We developed a method to capture total-body simian immunodeficiency virus (SIV) replication using immunoPET (antibody-targeted positron emission tomography). The administration of a poly(ethylene glycol)-modified, 64Cu-labeled SIV Gp120–specifc antibody led to readily detectable signals in the gastrointestinal and respiratory tract, lymphoid tissues and reproductive organs of viremic monkeys. Viral signals were reduced in aviremic antiretroviral-treated monkeys but detectable in colon, select lymph nodes, small bowel, nasal turbinates, the genital tract and lung. In elite controllers, virus was detected primarily in foci in the small bowel, select lymphoid areas and the male reproductive tract, as confirmed by quantitative reverse-transcription PCR (qRT-PCR) and immunohistochemistry. This real-time, in vivo viral imaging method has broad applications to the study of immunodeficiency virus pathogenesis, drug and vaccine development, and the potential for clinical translation.

ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

“…In the biodistribution analyses of infected animals, we found increased radioactive signals also in organs other than the infected lung. Signal enrichment in the liver might be due to nonspecific hepatic clearance of the radiolabeled antibody as seen by others (35), whereas nonspecific enrichment of radiolabeled antibody in kidney, blood, and spleen tissues has been reported in other immunoPET studies (33). Furthermore, in animals with IPA, it is likely that extracellular JF5 mannoprotein antigen released from infectious foci in the lungs accumulates in organs following shedding and circulation in the bloodstream, because the antigen is readily detectable in the serum of neutropenic animals and humans suffering from IPA (34,36,37).…”

“…ImmunoPET has recently been used for tracking simian immunodeficiency virus (SIV) infection in macaques (33), and our work is, to our knowledge, the first example of its exploitation in the rapid and specific detection of a lethal fungal infection. 18 F]FDG-PET results with no significant differences in the uptake of the lungs of A. fumigatus-infected animals compared with the lungs of control animals 48 hpi.…”

Total-Body PET: Maximizing Sensitivity to Create New Opportunities for Clinical Research and Patient Care

“…Such a paradigm could allow low-grade disease (cancer, inflammation, infection) to be detected and quantified. Tracers exist and continue to be developed for cancer and inflammation (35), and although specific tracers for a range of infectious agents (HIV, tuberculosis, malaria, parasites) are sorely needed, some are already in the pipeline (36).…”

Discordance in lymphoid tissue recovery following stem cell transplantation in rhesus macaques: an in vivo imaging study

“…Clearly, avenues need to be explored and developed to avoid immune responses to the radiotracer so that sequential imaging can be performed safely without the need of TBI. Along with pioneering attempts to provide noninvasive imaging to determine antiretroviral drug penetration 17 or SIV viral replication, 18 the methodology behind whole-body pharmacodynamics has advanced significantly in the past decade, appearing less futuristic. …”