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To evaluate the safety of [64Cu] Macrin and its whole-body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers. To detect [64Cu]-Macrin accumulation in sites of disease in subjects with cancer, sarcoidosis or myocardial infarct.
Macrophages are phagocytic cells of the innate immune system. Their accumulation is a hallmark of many inflammatory diseases and they have diverse roles in tissue responses to infection and injury and in tissue repair. As macrophages have a tissue specific and often disease stage specific roles, future therapies directed at macrophage subtypes at certain points in the course of a disease may be more efficacious and result in less systemic side effects, as compared to conventional chemotherapeutics. [64Cu] Macrin is designed to detect macrophages by PET imaging. As a result, PET imaging can be used to identify inflammatory "hotspots" and quantitate local macrophage density non-invasively. The investigators studies in mice showed that [64Cu] Macrin has excellent pharmacological and pharmacokinetic profile with high target uptake and low retention in background tissues and organs.
The investigators wish to first evaluate in healthy human subjects the pharmacological and pharmacokinetic profile, and the overall safety of the new radiopharmaceutical [64Cu] Macrin. The investigators will then establish the concentration of [64Cu] Macrin in patients following myocardial infarct, in sarcoidosis and in cancer patients. In a subset of patients where tissue sampling is feasible, we will correlate tracer uptake on imaging to macrophage density on histopathology or with additional standard of care imaging studies.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy Volunteers | Experimental | In 10 healthy volunteers the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. |
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| Cardiovascular Disease | Experimental | In 30 subjects with a history of recent myocardial infarct, the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. In addition, the ability of [64Cu] Macrin to concentrate at the infarct site will be correlated with cardiac MRI. |
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| Cancer | Experimental | In 30 subjects with an epithelial malignancy the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. In addition, the ability of [64Cu] Macrin to concentrate at the tumor site will be correlated with imaging and histopathology, where available. |
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| Sarcoidosis | Experimental | In 30 subjects with sarcoidosis the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied. In addition, the ability of [64Cu] Macrin to concentrate at the tumor site will be correlated with imaging and histopathology, where available. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [64]Cu Macrin | Drug | Up to 15 mCi of [68Ga]CBP8 will be administered to each subject. |
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| Measure | Description | Time Frame |
|---|---|---|
| To establish human dosimetry of 64Cu Macrin in Healthy Volunteers | We will use established methods to provide quantitative information on the amount of [64Cu] Macrin radioactivity that accumulates in peripheral organs and brain. Dose-corrected imaging data will be processed using time-activity curves based on ROIs manually-drawn on MR data and projected onto PET datasets. | 1 year |
| [64Cu] Macrin accumulation and detection in cancer | Probe uptake will be measured in organs affected by solid epithelial malignancies and compared to uptake in the uninvolved parts of the organs and in these organs in healthy volunteers. We expect greater uptake in the part of the organs affected by malignancy. | 1 year |
| [64Cu] Macrin accumulation and detection in myocardial infarction | Probe uptake will be measured at a myocardial infarct and compared to uptake in the remainder of the heart and in the hearts of healthy volunteers. We expect greater uptake at the site of a myocardial infarction. | 1 year |
| [64Cu] Macrin accumulation and detection in sarcoidosis | Probe uptake will be measured in the heart and lungs of patients with sarcoidosis and compared to uptake in these organs in healthy volunteers. We expect greater uptake in the organs affected by sarcoidosis. | 1 year |
| Measure | Description | Time Frame |
|---|---|---|
| [64Cu] Macrin accuracy for macrophage localization | To determine the sensitivity and specificity of [64 Cu] Macrin accumulation for the detection at sites of inflammation by comparing tracer accumulation to histopathology and/or standard of care imaging studies | 1 year |
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Inclusion Criteria:
Group 1: Healthy subjects
Must be 18 years of age or older
Must be deemed healthy at screening visit, as determined by the physician investigator or nurse practitioner, based on the following assessments at screening: physical examination, medical history and vital signs;
Group 2: Myocardial Infarction
Group 3: Sarcoidosis
Group 4: Malignancy
Exclusion Criteria:
• Electrical implants, such as cardiac pacemaker or perfusion pump;
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Recruiting | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41469153 | Derived | O'Shea A, Lewis AJM, Caravan P, Izquierdo-Garcia D, Le Fur M, Catalano OA, Montesi SB, Quintana JM, Carlson JCT, Dubach JM, Castro CM, Bobic M, Huesa-Berral C, Ng TSC, Bertolet A, Nahrendorf M, Weissleder R. First-in-Human Study of the Carbohydrate Nanoparticle 64Cu-Macrin. J Nucl Med. 2026 Mar 2;67(3):449-455. doi: 10.2967/jnumed.125.270770. |
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| ID | Term |
|---|---|
| D012507 | Sarcoidosis |
| D002318 | Cardiovascular Diseases |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006968 | Hypersensitivity, Delayed |
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Eligible subjects, including healthy volunteers and patients with sarcoidosis, cardiovascular disease and cancer, will be enrolled to undergo imaging with the PET Probe [64]Cu Macrin
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| Aileen O'Shea | Recruiting | Boston | Massachusetts | 02115 | United States |
|
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |