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Updated: Dec 24, 2025
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Development and characterization of CD54-targeted immunoPET imaging in solid tumors
Weijun Wei1,2, Dawei Jiang2, Hye Jin Lee3
1Department of Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 1630 Dongfang Rd, Shanghai, 200127, China.
Purpose:
Intercellular adhesion molecule-1 (ICAM-1, CD54) is an emerging therapeutic target for a variety of solid tumors including melanoma and anaplastic thyroid cancer (ATC). This study aims to develop an ICAM-1-targeted immuno-positron emission tomography (immunoPET) imaging strategy and assess its diagnostic value in melanoma and ATC models.
Methods:
Flow cytometry was used to screen ICAM-1-positive melanoma and ATC cell lines. Melanoma and ATC models were established using A375 cell line and THJ-16T cell line, respectively. An ICAM-1-specific monoclonal antibody (R6-5-D6) and a nonspecific human IgG were radiolabeled with 64Cu and the diagnostic efficacies were interrogated in tumor-bearing mouse models. Biodistribution and fluorescent imaging studies were performed to confirm the specificity of the ICAM-1-targeted imaging probes.
Results:
ICAM-1 was strongly expressed on melanoma and advanced thyroid cancer cell lines. 64Cu-NOTA-ICAM-1 immunoPET imaging efficiently delineated A375 melanomas with a peak tumor uptake of 21.28 ± 6.56 %ID/g (n = 5), significantly higher than that of 64Cu-NOTA-IgG (10.63 ± 2.58 %ID/g, n = 3). Moreover, immunoPET imaging with 64Cu-NOTA-ICAM-1 efficiently visualized subcutaneous and orthotopic ATCs with high clarity and contrast. Fluorescent imaging with IRDye 800CW-ICAM-1 also visualized orthotopic ATCs and the tumor uptake could be blocked by the ICAM-1 parental antibody R6-5-D6, indicating the high specificity of the developed probe. Finally, blocking with the human IgG prolonged the circulation of the 64Cu-NOTA-ICAM-1 in R2G2 mice without compromising the tumor uptake.
Conclusion:
ICAM-1-targeted immunoPET imaging could characterize ICAM-1 expression in melanoma and ATC, which holds promise for optimizing ICAM-1-targeted therapies in the future.
Insights
This study developed an ICAM-1-targeted immunoPET imaging strategy for melanoma and anaplastic thyroid cancer (ATC). The novel imaging approach successfully visualized tumors, demonstrating its potential for guiding ICAM-1-targeted therapies.
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.
