PET Imaging of Radiolabeled Anti-HIV-1 Envelope Monoclonal Antibody (VRC01)

This will be a single-center pilot study to determine dosimetry and tissue
uptake/distribution and pharmacokinetics of 89Zr-VRC01. Up to 18 uninfected and HIV-infected
subjects who are either taking or not taking ART will receive a small IV dose of 89Zr-VRC01.
After administration of IV 89Zr-VRC01, subjects will undergo up to 4 whole body PET/MR
imaging at 2, 6, 24 and 72-120h to determine the pharmacokinetics and radiation dose
exposure. The study involves two phases with the second phase only to be performed only if a
difference between PET activity in one or more region of interest can be determined between
participant groups Phase I (HIV infected, viremic participants and healthy volunteers).
Initially, up to 6 individuals with plasma HIV RNA levels >1,000 copies/ml and up to 6
HIV-uninfected individuals will be administered 89Zr radiolabeled VRC01 followed by PET-MR
imaging as above (Phase 1). If differences in PET activity in one or more imaging region of
interest can be identified between infected and uninfected individuals, up to 6 individuals
on suppressive ART will be administered 89Zr radiolabeled VRC01 followed by PET-MRI (Phase
2). Timing of the PET-MR scans will be determined based on the data from Phase 1.

Inclusion Criteria:

Study Phase 1

1. Age ≥18 years, and

2. HIV uninfected, or

3. HIV infection, and

4. has an HIV viral load measurement within 12 months of study entry of >40 copies/mL,
and

5. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01
binding activity (HIV infected participants only)

Study Phase 2

1. Age ≥18 years, and

2. HIV infection, and

3. Initiated a combination ART regimen and has HIV viral load measurements below the
detection limit of a clinically approved PCR-based assay (e.g. <40 HIV-1 RNA copies/mL
of blood), and

4. HIV-1 envelope RNA or DNA consensus sequence from peripheral blood suggestive of VRC01
binding activity

Exclusion Criteria:

Study Phase 1

1. For patients planning to be imaged on PET-MR scanner, exclusion criteria will include
any contra-indication to MRI, including permanent pacemaker, implantable metallic
device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia

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

3. Patients who have had a study involving radiation within six months of enrolling in
this study

4. Patients who are pregnant (female patients of childbearing age will be tested prior to
injection of imaging agent - positive test will exclude from participating in the
study)

5. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <70,000
cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <40 mL/minute,
aspartate aminotransferase >100 units/L, alanine aminotransferase >100 units/L.

6. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)

7. Serious illness requiring hospitalization or parental antibiotics within the preceding
3 months.

8. Current HIV-related opportunistic infection such as pneumocystis pneumonia,
disseminated microbacterial infection, invasive cryptococcal disease, candidal
esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis

Study Phase 2

1. For patients planning to be imaged on PET-MR scanner, exclusion criteria will include
any contra-indication to MRI, including permanent pacemaker, implantable metallic
device/ prosthetic, aneurysm clip, non-removable piercing, or severe claustrophobia

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

3. Patients who have had a study involving radiation within 12 months of enrolling in
this study

4. Patients who are pregnant (female patients of childbearing age will be tested prior to
injection of imaging agent - positive test will exclude from participating in the
study)

5. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <70,000
cells/mm3, hemoglobin < 8 mg/dL, estimated creatinine clearance <40 mL/minute,
aspartate aminotransferase >100 units/L, alanine aminotransferase >100 units/L.

6. Absolute CD4+ T cell count <100 cells/μL (HIV infected individuals only)

7. Serious illness requiring hospitalization or parental antibiotics within the preceding
3 months.

8. Current HIV-related opportunistic infection such as pneumocystis pneumonia,
disseminated microbacterial infection, invasive cryptococcal disease, candidal
esophagitis (limited oral thrush acceptable) and cerebral toxoplasmosis