First-in-Human Study of the Carbohydrate Nanoparticle ⁶⁴Cu-Macrin.

Area of Science:

• Immunology
• Nuclear Medicine
• Radiochemistry

Background:

• Macrophage density and phenotype are crucial in innate immunity, influencing cancer and autoimmune disease progression.
• Quantifying macrophages spatially and temporally could lead to targeted therapies.
• Macrin, a nanoparticle, demonstrated selective macrophage accumulation in preclinical models.

Purpose of the Study:

• Evaluate the biodistribution, dosimetry, and safety of ⁶⁴Cu-labeled Macrin in humans.
• Explore its potential for imaging inflammatory and malignant conditions.
• Assess ⁶⁴Cu-Macrin as a PET imaging agent for macrophage-rich tissues.

Main Methods:

• A first-in-human study (NCT04843891) involving 10 participants (7 healthy, 3 patients).
• Single administration of ⁶⁴Cu-Macrin (approx. 444 MBq).
• Serial PET/CT scans for biodistribution and dosimetry, blood sampling for pharmacokinetics, and adverse event monitoring.

Main Results:

• ⁶⁴Cu-Macrin was found to be safe with no adverse effects observed.
• Biphasic blood clearance with half-lives of 1.3 h (fast) and 22.3 h (slow).
• Significant accumulation of ⁶⁴Cu-Macrin observed at active disease sites in cancer and sarcoidosis patients.

Conclusions:

• ⁶⁴Cu-Macrin PET imaging is safe with favorable pharmacokinetics.
• The tracer effectively accumulates in macrophage-rich tissues, including sites of cancer and sarcoidosis.
• This imaging approach shows promise for patient stratification and assessing therapy response in macrophage-targeted treatments.