Interrogating the Theranostic Capacity of a MUC16-Targeted Antibody for Ovarian Cancer

huAR9.6 can differentiate between OC cells with high and low MUC16 expression in vitro and in vivo. (A) Radioligand cell-binding assay with [⁸⁹Zr]Zr-DFO-huAR9.6 in cell lines with varying levels of MUC16 expression. Binding was significantly reduced with administration of 1,000-fold excess blocking dose of nonlabeled huAR9.6. (B) In vitro validation of huAR9.6-AF488 binding in OC cells via flow cytometry. (C) huAR9.6 immunohistochemical staining images of harvested OVCAR3, OVCAR4, OVCAR5, and OVCAR8 subcutaneous tumors. Arrow indicates MUC16 expression on surface of OVCAR5 cells. (D) Female nude mice containing subcutaneous tumors that were injected with 7.4–9.25 MBq (20–25 μg) of [⁸⁹Zr]Zr-DFO-huAR9.6 followed by PET imaging. (E) Terminal biodistributions at 144 h after injection. n = 3 for OVCAR4 and OVCAR8; n = 4 for OVCAR3 and OVCAR5. *P ≤ 0.05. ***P ≤ 0.001. ****P ≤ 0.0001. %ID = percentage injected dose; FSC-A = forward scatter area; T = tumor.

[¹⁷⁷Lu]Lu-CHX-A″-DTPA-huAR9.6 treatment improves overall survival and inhibits tumor growth in OVCAR3-bearing mice. (A and B) Overall survival percentage (A) and TV (mm³) growth curves (B) of R2G2 OVCAR3-bearing mice after treatment. Significant tumor growth inhibition was observed in all treated mice in comparison to saline and IgG isotype controls. Shading represents 95% CI. ***P ≤ 0.001. ****P ≤ 0.0001.

[¹⁷⁷Lu]Lu-CHX-A″-DTPA-huAR9.6 still shows strong antitumor effects in recurrent tumors. (A) 72-h PET/CT imaging with [⁸⁹Zr]Zr-DFO-huAR9.6 shows that OVCAR3 recurrent tumors still strongly express MUC16. Images are represented as maximum-intensity projections. (B) Individual TVs for recurrent OVCAR3 tumors. Mice were retreated with 9.25 MBq of [¹⁷⁷Lu]Lu-CHX-A″-DTPA-huAR9.6 at day 75 of therapy. %ID = percentage injected dose; MIP = maximum-intensity projection; T = tumor.