Development and characterization of CD54-targeted immunoPET imaging in solid tumors

Area of Science:

• Oncology
• Medical Imaging
• Molecular Biology

Background:

• Intercellular adhesion molecule-1 (ICAM-1, CD54) is a key therapeutic target in solid tumors like melanoma and anaplastic thyroid cancer (ATC).
• Developing targeted imaging strategies is crucial for effective diagnosis and treatment planning.

Purpose of the Study:

• To create and evaluate an ICAM-1-targeted immuno-positron emission tomography (immunoPET) imaging strategy.
• To assess the diagnostic utility of this strategy in preclinical models of melanoma and ATC.

Main Methods:

• Screening of ICAM-1-positive melanoma and ATC cell lines using flow cytometry.
• Development of melanoma (A375) and ATC (THJ-16T) mouse models.
• Radiolabeling of an ICAM-1-specific antibody (R6-5-D6) and a nonspecific IgG with ⁶⁴Cu for immunoPET imaging.
• Biodistribution and fluorescent imaging studies to confirm probe specificity.

Main Results:

• ⁶⁴Cu-NOTA-ICAM-1 immunoPET demonstrated efficient delineation of melanomas with significantly higher tumor uptake compared to control IgG.
• ImmunoPET imaging clearly visualized subcutaneous and orthotopic ATCs.
• Fluorescent imaging confirmed high specificity of the ICAM-1-targeted probe, with tumor uptake blocked by the parental antibody.

Conclusions:

• ICAM-1-targeted immunoPET imaging effectively characterizes ICAM-1 expression in melanoma and ATC.
• This imaging approach shows promise for optimizing future ICAM-1-targeted therapeutic strategies.