Development of [111In]In-CHX-A″-DTPA-αCD68 for ImmunoSPECT to Image Murine Macrophages

Area of Science:

• Oncology
• Radiochemistry
• Immunology

Background:

• High tumor-associated macrophage (TAM) abundance correlates with poor prognosis in renal cell carcinoma (RCC).
• CD68 is a key biomarker for macrophages, present in both preclinical models and human tissues.
• Noninvasive quantification of TAMs is crucial for assessing disease progression and treatment efficacy.

Purpose of the Study:

• To develop and validate an anti-mouse CD68 (mCD68) immunoSPECT imaging agent for in vivo TAM quantification in RCC.
• To assess the agent's ability to monitor response to macrophage-modulating therapies in a preclinical RCC model.

Main Methods:

• Synthesis and characterization of [¹¹¹In]In-CHX-A″-DTPA-αCD68 for binding affinity, stability, and specificity.
• In vivo biodistribution and immunoSPECT imaging in a Renca syngeneic RCC model.
• Correlation of immunoSPECT signal with ex vivo CD68 expression via flow cytometry and assessment of treatment response.

Main Results:

• The [¹¹¹In]In-CHX-A″-DTPA-αCD68 agent demonstrated high binding affinity and specificity for CD68.
• ImmunoSPECT signal strongly correlated with ex vivo CD68 expression in tumors and spleens (r=0.854).
• The agent successfully detected a reduction in TAM burden following anti-CSF1R treatment, correlating with ex vivo findings (r=0.952).

Conclusions:

• This study presents the first successful in vivo immunoSPECT imaging of CD68.
• ImmunoSPECT imaging of CD68 offers a direct, noninvasive method for assessing total TAM burden in RCC.
• This approach is translatable for monitoring macrophage-modulating treatment responses in preclinical settings.