Clinical trial NCT04843891: 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
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Sarcoid
Cardiovascular Diseases
Cancer
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2021-04-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention 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
Primary purpose: DIAGNOSTIC

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.

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.

Primary outcomes:
measure: To establish human dosimetry of 64Cu Macrin in Healthy Volunteers
timeFrame: 1 year
measure: [64Cu] Macrin accumulation and detection in cancer
timeFrame: 1 year
measure: [64Cu] Macrin accumulation and detection in myocardial infarction
timeFrame: 1 year
measure: [64Cu] Macrin accumulation and detection in sarcoidosis
timeFrame: 1 year
Secondary outcomes:
measure: [64Cu] Macrin accuracy for macrophage localization
timeFrame: 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Aileen O'Shea
state: Massachusetts
Study officials:
References: