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

Primary Purpose

Sarcoid, Cardiovascular Diseases, Cancer

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
[64]Cu Macrin
Sponsored by
Ralph Weissleder, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Sarcoid

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts 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.

Sites / Locations

  • Massachusetts General HospitalRecruiting
  • Aileen O'SheaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Healthy Volunteers

Cardiovascular Disease

Cancer

Sarcoidosis

Arm Description

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

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
[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.
[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.
[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.

Secondary Outcome Measures

[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

Full Information

First Posted
March 31, 2021
Last Updated
June 22, 2022
Sponsor
Ralph Weissleder, MD
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1. Study Identification

Unique Protocol Identification Number
NCT04843891
Brief Title
Evaluation of PET Probe [64]Cu-Macrin in Cardiovascular Disease, Cancer and Sarcoidosis.
Official Title
Preliminary Evaluation of [64Cu] Macrin in Healthy Individuals and Subjects With Cardiovascular Disease, Sarcoidosis and Malignancy.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 6, 2021 (Actual)
Primary Completion Date
April 5, 2023 (Anticipated)
Study Completion Date
April 5, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ralph Weissleder, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoid, Cardiovascular Diseases, Cancer

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Healthy Volunteers
Arm Type
Experimental
Arm Description
In 10 healthy volunteers the radiation dosimetry, normal organ distribution, and safety of [64Cu]-Macrin injection will be studied.
Arm Title
Cardiovascular Disease
Arm Type
Experimental
Arm 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.
Arm Title
Cancer
Arm Type
Experimental
Arm 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.
Arm Title
Sarcoidosis
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
[64]Cu Macrin
Intervention Description
Up to 15 mCi of [68Ga]CBP8 will be administered to each subject.
Primary Outcome Measure Information:
Title
To establish human dosimetry of 64Cu Macrin in Healthy Volunteers
Description
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.
Time Frame
1 year
Title
[64Cu] Macrin accumulation and detection in cancer
Description
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.
Time Frame
1 year
Title
[64Cu] Macrin accumulation and detection in myocardial infarction
Description
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.
Time Frame
1 year
Title
[64Cu] Macrin accumulation and detection in sarcoidosis
Description
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.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
[64Cu] Macrin accuracy for macrophage localization
Description
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
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ralph Weissleder, MD, PhD
Phone
617-726-8226
Email
RWEISSLEDER@PARTNERS.ORG
Facility Name
Aileen O'Shea
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aileen O'Shea, MD
Phone
857-250-9201
Email
aoshea1@mgh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Andrew Lewis, MD
Email
ALEWIS33@mgh.harvard.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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

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