Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis.

Ralph Weissleder, MD

Status and phase: Enrolling; Phase 1

Conditions: Sarcoid; Cardiovascular Diseases; Cancer

Treatments: Drug: [64]Cu Macrin

Study type: Interventional

Funder types: Other

Identifiers

NCT04843891

2021P000355

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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;

  • No known history of pre-existing cardiac or respiratory disease or malignancy
  • Have the ability to give written informed consent.

Group 2: Myocardial Infarction

• History of percutaneous coronary intervention (PCI) for acute or chronic coronary syndrome (within 3-5 days)
• Have the ability to give written informed consent
• Must be 18 years of age or older
• Hemodynamically stable

Group 3: Sarcoidosis

• A suspected or confirmed diagnosis of intrathoracic sarcoidosis
• Have the ability to give written informed consent
• Must be 18 years of age or older

Group 4: Malignancy

• Suspected or confirmed thoracic, intra-abdominal or pelvic malignancy
• Have the ability to give written informed consent
• Must be 18 years of age or older

Exclusion criteria

• • Electrical implants, such as cardiac pacemaker or perfusion pump;

  • Ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, metallic tattoos anywhere on the body, tattoos near the eye, or steel implants ferromagnetic objects such as jewelry or metal clips in clothing;
  • eGFR of less than 30 mL/min/1.73 m2 within the past 30 days;
  • Pregnant or breastfeeding (a negative quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
  • Self-reported or documented claustrophobic reactions;
  • Research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
  • Unable to lie comfortably on a bed inside the MR-PET;
  • BMI > 33 (limit of the PET-MRI table);
  • Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures);
  • Stroke within the last 3 months;
  • Cardiac or major surgery within the last 3 months;
  • History of abnormal heart rate including persistent tachyarrhythmia (heart rate persistently >120 bpm) or bradyarrhythmia (heart rate persistently < 50 bpm);
  • History of atrial premature complexes with daytime pauses > 3s;
  • Contraindications to gadolinium-based contrast agents, including an eGFR < 30 mL/min (myocardial infarction and sarcoidosis patients only).
  • History of myeloproliferative disorder.
  • Age >80 years.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 4 patient groups

Healthy Volunteers

Experimental group

Description:

In 10 healthy volunteers the radiation dosimetry, normal organ distribution, and safety of \[64Cu\]-Macrin injection will be studied.

Treatment:

Drug: [64]Cu Macrin

Cardiovascular Disease

Experimental group

Description:

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.

Treatment:

Drug: [64]Cu Macrin

Cancer

Experimental group

Description:

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.

Treatment:

Drug: [64]Cu Macrin

Sarcoidosis

Experimental group

Description:

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.

Treatment:

Drug: [64]Cu Macrin