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

NCT ID: NCT04843891

Last Updated: 2022-06-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-06
• Study Completion Date: 2023-04-05

Brief Summary

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.

Detailed 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.

Conditions

Sarcoid; Cardiovascular Diseases; Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Healthy Volunteers

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

Group Type: EXPERIMENTAL

[64]Cu Macrin

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

Cardiovascular Disease

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.

Group Type: EXPERIMENTAL

[64]Cu Macrin

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

Cancer

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.

Group Type: EXPERIMENTAL

[64]Cu Macrin

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

Sarcoidosis

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.

Group Type: EXPERIMENTAL

[64]Cu Macrin

Intervention Type: DRUG

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

Interventions

[64]Cu Macrin

Up to 15 mCi of \[68Ga\]CBP8 will be administered to each subject.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ralph Weissleder, MD

OTHER

Sponsor Role: lead

Responsible Party

Ralph Weissleder, MD

Professor of Radiology

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Aileen O'Shea

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Ralph Weissleder, MD, PhD

Role: primary

RWEISSLEDER@PARTNERS.ORG

617-726-8226

Aileen O'Shea, MD

Role: primary

aoshea1@mgh.harvard.edu

857-250-9201

Andrew Lewis, MD

Role: backup

ALEWIS33@mgh.harvard.edu

Other Identifiers

2021P000355

Identifier Type: -

Identifier Source: org_study_id