Application of IV 99mTc-tilmanocept for Imaging of Macrophage-specific Inflammation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate uptake of intravenously administered 99mTc-tilmanocept using single photon emission computed tomography (SPECT/CT) scanning in individuals with HIV and individuals without HIV.

Detailed Description
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People living with HIV (PLWH) have an increased risk of cardiovascular disease (CVD) compared to individuals without HIV. Increased systemic immune activation and arterial inflammation are thought to contribute to this increased risk by affecting the highly inflammatory process of atherosclerotic plaque formation and progression. This study will evaluate whether intravenous administration of a macrophage-specific imaging agent, 99mTc-tilmanocept, followed by SPECT/CT scanning can permit quantification of aortic 99mTc-tilmanocept uptake, reflective of aortic macrophage-specific inflammation among participants with HIV. We will also compare aortic 99mTc-tilmanocept uptake in participants with HIV to participants without HIV. Immunology parameters such as markers of immune activation and traditional CVD parameters will be assessed in relation to imaging assessments.

Official Title
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Application of IV 99mTc-tilmanocept for Imaging of Macrophage-specific Inflammation

Conditions
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HIV

Intervention / Treatment
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* Diagnostic Test: Imaging


Participation Criteria
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Eligibility Criteria
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HIV-infected participants: Inclusion Criteria: men and women, ages 18 to 80, with documented HIV infection current use of antiretroviral therapy (ART), with no changes to regimen within last 3 months Exclusion Criteria: pregnancy or breastfeeding known active opportunistic infection requiring ongoing medical therapy (not including Hepatitis B/C) CD4 count < 50 cells/mm3 history of myocardial infarction,acute coronary syndrome, or coronary artery stenting or surgery stable or unstable angina recent and/or current treatment with prescription, systemic steroids or anti-inflammatory/immune suppressant medical therapies current use of statin or use of statin for > 1 month within the last 6 months known allergy to dextrans and/or DTPA and/or radiometals eGFR < 60 ml/min/1.73 m2 calculated by CKD-EPI known severe allergy to iodinated contrast media contraindication to nitroglycerin significant radiation exposure (>2 CT angiograms) received within the past 12 months reported active illicit drug use concurrent enrollment in another research study judged by the study investigators to interfere with the current study Non-HIV-infected participant: Inclusion criteria: -men and women, ages 18 to 80, without HIV infection Exclusion Criteria: pregnancy or breastfeeding history of myocardial infarction, acute coronary syndrome, or coronary artery stenting or surgery stable or unstable angina recent and/or current treatment with prescription, systemic steroids or anti-inflammatory/immune suppressant medical therapies current use of statin or use of statin for > 1 month within the last 6 months known allergy to dextrans and/or DTPA and/or radiometals eGFR < 60 ml/min/1.73 m2 calculated by CKD-EPI known severe allergy to iodinated contrast media contraindication to nitroglycerin significant radiation exposure (>2 CT angiograms) received within the past 12 months reported active illicit drug use concurrent enrollment in another research study judged by the study investigators to interfere with the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HIV-infected<br> | Diagnostic Test: Imaging<br>* Macrophage-specific inflammation<br>|
| non-HIV-infected<br> | Diagnostic Test: Imaging<br>* Macrophage-specific inflammation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic uptake of intravenously administered 99mTc tilmanocept on SPECT/CT |  | within 6 weeks of screening visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aortic plaque burden and morphology on CT angiography | Aortic plaque burden and morphology will be assessed through measurement of total, calcified, and non-calcified aortic plaque volume (mm3). | within 6 weeks of screening visit | 
| Traditional markers of cardiovascular disease (CVD) risk in relation to cardiovascular imaging outcomes | We will calculate a risk score of future CVD risk (%) which will take into account traditional markers of CVD risk such as blood pressure, lipid levels, and age. | within 6 weeks of screening visit | 
| Inflammatory markers in relation to cardiovascular imaging outcomes | The following inflammatory markers will be evaluated: soluble CD163 (ng/ml) , soluble CD 14 (ng/ml) , and Lp-PLA2 (ng/ml). | within 6 weeks of screening visit | 
| Imaging assessments of the coronary vasculature | Cardiac CT angiography will be used to assess the coronary vasculature. Total, calcified, and non-calcified coronary plaque volume (mm3) will be measured. | within 6 weeks of screening visit | 
| Comparison of imaging assessments between HIV-infected participants and non-HIV-infected participants | We will compare the standardized uptake values on SPECT/CT of HIV-infected participants and non-HIV-infected participants. | within 6 weeks of screening visit | 
| Uptake of intravenously administered 99mTc tilmanocept on SPECT/CT in regions other than the aorta | Uptake of tilmanocept on SPECT/CT will determined by calculating a standardized uptake value. | within 6 weeks of screening visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Macrophage-specific inflammation, Arterial inflammation, Neuroinflammation, SPECT/CT, Tilmanocept