TY - JOUR
T1 - PET and Optical Imaging of Caveolin-1 in Gastric Tumors
AU - Surendra Panikar, Sandeep
AU - Shmuel, Shayla
AU - Lewis, Jason S.
AU - Pereira, Patrícia M.R.
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/10/3
Y1 - 2023/10/3
N2 - Previous studies have suggested tumoral caveolin-1 (CAV1) as a predictive biomarker for the response to anti-HER2 antibody drug therapies in gastric tumors. In this study, radiolabeled and fluorescently labeled anti-CAV1 antibodies were developed and tested as an immunoPET or optical imaging agent to detect CAV1 in HER2-positive/CAV1-high NCIN87 gastric tumors. The expression of CAV1 receptors in NCIN87 gastric tumors and nontumor murine organs was determined by Western blot. Binding assays were performed to validate the anti-CAV1 antibody specificity for CAV1-expressing NCIN87 cancer cells. Subcutaneous and orthotopic NCIN87 xenografts were used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Additional HER2-PET and CAV1-optical imaging was also performed to determine CAV1 in the HER2-positive tumors. 89Zr-labeled anti-CAV1 antibody was able to bind to CAV1-expressing NCIN87 cells with a Bmax value of 2.7 × 103 CAV1 receptors/cell in vitro. ImmunoPET images demonstrated the localization of the antibody in subcutaneous NCIN87 xenografts. In the orthotopic model, CAV1 expression was also observed by optical imaging in the HER2-positive tumors previously imaged with HER2-PET. Ex vivo biodistribution analysis further confirmed these imaging results. The preclinical data from this study demonstrate the potential of using CAV1-PET and optical imaging for detecting gastric tumors.
AB - Previous studies have suggested tumoral caveolin-1 (CAV1) as a predictive biomarker for the response to anti-HER2 antibody drug therapies in gastric tumors. In this study, radiolabeled and fluorescently labeled anti-CAV1 antibodies were developed and tested as an immunoPET or optical imaging agent to detect CAV1 in HER2-positive/CAV1-high NCIN87 gastric tumors. The expression of CAV1 receptors in NCIN87 gastric tumors and nontumor murine organs was determined by Western blot. Binding assays were performed to validate the anti-CAV1 antibody specificity for CAV1-expressing NCIN87 cancer cells. Subcutaneous and orthotopic NCIN87 xenografts were used for PET imaging and ex vivo biodistribution of the radioimmunoconjugate. Additional HER2-PET and CAV1-optical imaging was also performed to determine CAV1 in the HER2-positive tumors. 89Zr-labeled anti-CAV1 antibody was able to bind to CAV1-expressing NCIN87 cells with a Bmax value of 2.7 × 103 CAV1 receptors/cell in vitro. ImmunoPET images demonstrated the localization of the antibody in subcutaneous NCIN87 xenografts. In the orthotopic model, CAV1 expression was also observed by optical imaging in the HER2-positive tumors previously imaged with HER2-PET. Ex vivo biodistribution analysis further confirmed these imaging results. The preclinical data from this study demonstrate the potential of using CAV1-PET and optical imaging for detecting gastric tumors.
UR - http://www.scopus.com/inward/record.url?scp=85174830627&partnerID=8YFLogxK
U2 - 10.1021/acsomega.3c03614
DO - 10.1021/acsomega.3c03614
M3 - Article
C2 - 37810678
AN - SCOPUS:85174830627
SN - 2470-1343
VL - 8
SP - 35884
EP - 35892
JO - ACS Omega
JF - ACS Omega
IS - 39
ER -