PET-MR Imaging with [18F]F-AraG for HIV Infection

Overseen By Steven J Deeks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: CellSight Technologies, Inc.

Must not be taking: Immune modifying therapy

Disqualifiers: Pregnancy, Breastfeeding, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging agent called [18F]F-AraG to understand its distribution in individuals with HIV. The goal is to determine how this agent can visualize areas affected by the infection using advanced imaging techniques. It targets people living with HIV, particularly those who haven't started or recently paused antiretroviral therapy, or have high viral levels in their blood. Participants have the opportunity to contribute to HIV research through cutting-edge medical imaging. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants who have not been on antiretroviral therapy (ART) for at least 1 week prior to the study can be enrolled. It is recommended to discuss your current medications with the study team.

What prior data suggests that this imaging method is safe for humans?

Research has shown that \[18F\]F-AraG is a new substance used in PET-MR scans to monitor immune system activity. Studies have demonstrated that \[18F\]F-AraG can be safely prepared and used for imaging. Early results suggest it is generally well-tolerated, with no major side effects reported so far.

This trial is in its early stages, focusing primarily on understanding the treatment's safety and how it works in the body. Participants receive small doses and undergo close monitoring. Since \[18F\]F-AraG is mainly used for imaging, the risks might be lower compared to treatments requiring larger doses or long-term use. However, as with any new treatment, unknown risks may still exist. Participants are closely watched for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard HIV treatments that focus on suppressing the virus with antiretroviral therapy, [18F]F-AraG is unique because it serves as a radiofluorinated imaging agent. This agent, known by its trade name VisAcT, uses a novel active ingredient—2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine—to provide detailed images of immune activity. Researchers are excited about this treatment because it offers a new way to visualize and understand the immune response to HIV infection in real-time, potentially leading to better-informed treatment decisions and personalized care strategies.

What evidence suggests that this imaging method is effective for determining the anatomical distribution of the PET tracer in HIV?

Research has shown that [18F]F-AraG, which participants in this trial will receive, serves as a special imaging tool to visualize immune activity in people with HIV. Studies have found that this tool can be safely used in humans and provides clear images of immune system function. It highlights areas in the body where the immune system is active, aiding doctors in understanding how HIV persists. This insight might lead to better treatment options. Early results suggest that [18F]F-AraG effectively shows where the virus is active, even during treatment. ^{2 4 6 7 8}

Who Is on the Research Team?

Timothy J Henrich, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

Adults over 18 with HIV, either treated early/late or not on antiretroviral therapy (ART), can join. They must understand the consent form and meet certain health criteria like a specific platelet count, liver enzyme levels, and kidney function. People with MRI contraindications, recent immune therapies, pregnancy/breastfeeding, transplants, severe infections or illnesses within 3 months are excluded.

Inclusion Criteria

Aspartate aminotransferase (AST) <2 x ULN

Ability to read and understand written informed consent document

I have HIV and am either on ART, have never been on ART, or haven't taken ART for at least a month.

Exclusion Criteria

Any contra-indication to MRI, including permanent pacemaker, implantable metallic device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia

Any medical condition that would compromise the imaging acquisition, in the opinion of the investigator

I do not have severe HIV-related infections like pneumonia or brain infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Imaging

Participants receive one intravenous microdose of [18F]F-AraG followed by whole-body PET-MR imaging to determine the anatomical distribution of the PET tracer

1 day

1 visit (in-person)

Follow-up

Participants are monitored for any immediate reactions and to correlate [18F]F-AraG uptake with measures of HIV persistence

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F]F-AraG

Trial Overview The trial is testing [18F]F-AraG via PET-MR imaging to see where it goes in the body of HIV-infected individuals. It's an exploratory study at one center involving a single microdose of this tracer followed by whole-body scans to map its distribution.

How Is the Trial Designed?

Group I: [18F]F-AraG Experimental Treatment 1 Intervention

radiofluorinated imaging agent, \[18F\]F-AraG (2'-deoxy-2'-fluoro-9-β-D-arabinofuranosylguanine) Trade name: VisAcT

Who Is Running the Clinical Trial?

CellSight Technologies, Inc.

Lead Sponsor

Trials

18

Recruited

320+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

The study involving six healthy volunteers demonstrated that the radiolabeled nucleoside analog [18F]F-AraG is well tolerated, with no adverse effects reported after administration, indicating its safety for use in imaging.

Biodistribution results showed that [18F]F-AraG primarily accumulates in the kidneys and liver, aligning with its mechanism of action related to mitochondrial metabolism, making it a promising tracer for various applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. Levi, J., Duan, H., Yaghoubi, S., et al.[2022]

A novel PET radiotracer, [18F]F-AraG, can detect activated T cells in aGVHD before clinical symptoms appear, potentially allowing for earlier diagnosis and treatment.

In a murine model, [18F]F-AraG PET imaging successfully visualized activated donor T cells in secondary lymphoid organs, indicating its effectiveness for monitoring aGVHD and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Ronald, JA., Kim, BS., Gowrishankar, G., et al.[2018]

Three novel radiolabeled O(6)-benzylguanine derivatives were developed as potential PET imaging agents for breast cancer, specifically targeting the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT).

These new compounds could improve the detection and understanding of breast cancer by providing insights into the activity of AGT, which plays a crucial role in DNA repair mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and preliminary biological evaluation of 6-O-[11C]-[(methoxymethyl)benzyl]guanines, new potential PET breast cancer imaging agents for the DNA repair protein AGT. Liu, X., Zheng, QH., Fei, X., et al.[2019]

The novel imaging agent [(18)F]F-AraG was successfully synthesized with a radiochemical yield of 7-10%, demonstrating potential for use in positron emission tomography (PET) imaging of T cells.

Preliminary studies indicate that both leukemia cell lines and activated primary thymocytes effectively take up [(18)F]F-AraG, supporting its future application in imaging T-cell activity in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. Namavari, M., Chang, YF., Kusler, B., et al.[2021]

The PET tracer [18 F]F-AraG is effective for visualizing activated T cells, which could be beneficial in studying various diseases.

A simplified protocol for preparing this PET tracer has been developed, allowing for easier access and use in preclinical research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simplified and accessible [18 F]F-AraG synthesis procedure for preclinical PET. Högnäsbacka, AA., Cortés González, MA., Halldin, C., et al.[2023]

The study successfully developed a radiolabeled version of dolutegravir ([18F]DTG) for use in positron emission tomography (PET) imaging, achieving high purity and yield, which is crucial for safe in vivo applications.

PET imaging with [18F]DTG in a healthy macaque demonstrated its potential to visualize drug distribution and elimination routes, paving the way for future research on HIV-1 interactions in infected cell reservoirs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging. Tisseraud, M., Goutal, S., Bonasera, T., et al.[2023]

Citations

1. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT03684655

Imaging Immune Activation in HIV by PET-MR This is a single center exploratory imaging study involving one intravenous microdose of [18F]F-AraG followed by whole-body positron ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6751256/

Seeing Is Believing: Nuclear Imaging of HIV Persistence - PMC In this review, we discuss past and current nuclear imaging approaches that have been applied to HIV infection with an emphasis on current strategies.

3. withpower.com withpower.com/trial/phase-1-hiv-infections-8-2018-ca3f0

PET-MR Imaging with [18F]F-AraG for HIV Infection In studies with healthy volunteers, [18F]F-AraG showed favorable safety and radiation levels, indicating it is generally safe for human use.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20838911/

deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine: a novel ... To test the possibility of using a radiofluorinated AraG as an imaging agent, we have synthesized 2'-deoxy-2'-[(18)F]fluoro-9-β-D-arabinofuranosylguanine ([(18) ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/hiv-aids

UCSF HIV/AIDS Clinical Trials — San Francisco Bay Area This is a single center exploratory imaging study involving one intravenous microdose of [18F]F-AraG followed by whole-body positron emission ...

6. nature.com nature.com/articles/s42003-024-06494-x

[18F]F-AraG imaging reveals association between ... This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue.

7. reporter.nih.gov reporter.nih.gov/search/EaC3BhVN6USBfOMuTswDVQ/project-details/11094065

RePORT ⟩ RePORTER We're sorry but RePORTER doesn't work properly without JavaScript enabled. Please enable it to continue.

8. profiles.stanford.edu profiles.stanford.edu/benjamin-franc

Benjamin Lewis Franc - Stanford Profiles Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways ...