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

Trial Summary

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.

Is [18F]F-AraG safe for use in humans?

In studies with healthy volunteers, [18F]F-AraG showed favorable safety and radiation levels, indicating it is generally safe for human use. ^{1 2 3 4 5}

How is the drug [18F]F-AraG different from other treatments for HIV?

[18F]F-AraG is unique because it is a PET imaging agent that specifically targets activated T cells, allowing for visualization of immune activity in the body. This is different from standard HIV treatments, which typically focus on suppressing the virus rather than imaging immune responses. ^{1 2 4 5 6}

What is the purpose of this trial?

This is a single center exploratory imaging study involving one intravenous microdose of \[18F\]F-AraG followed by whole-body positron emission tomography-magnetic resonance (PET-MR) imaging in HIV infected individuals to determine the anatomical distribution of the PET tracer. Participants will be enrolled if they were treated during early or late HIV infection. In addition, individuals not on antiretroviral therapy (ART) or with HIV-1 plasma RNA levels \>5,000 copies/mL will be enrolled. Up to 30 participants will be enrolled with HIV.

Research Team

Timothy J Henrich, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

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

Participants who are breastfeeding

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Simplified and accessible [18 F]F-AraG synthesis procedure for preclinical PET. [2023]

3. England 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. [2019]

4. United States 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. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Biodistribution of a Mitochondrial Metabolic Tracer, [18F]F-AraG, in Healthy Volunteers. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging. [2023]