Figure 3.

ImmunoPET delineates the uptake of [⁸⁹Zr]Zr-DFO-muAR9.6 in orthotopic-turned-metastatic and PDX models of HGSOC. A, PET images (MIPs scaled 0–100) of female nude mice taken 6 weeks after surgical implantation of the left ovary with OVCAR3 cells. ImmunoPET imaging with 1 mg/kg of [⁸⁹Zr]Zr-DFO-muAR9.6 (210 ± 11.7 μCi; 7.8 ± 0.4 MBq; 24 μg) delineated the orthotopic tumor as well as a lymph node in the hepatic region. B, Periodic immunoPET imaging of a mouse bearing an orthotopic OVCAR3 xenograft showed disease progression from the primary site of tumor cell inoculation (left ovary) to the liver and distant sites including the mediastinal lymph nodes in the thorax and the lumbar aortic lymph node in the lower abdomen. In this experiment, the mouse was injected three times with [⁸⁹Zr]Zr-DFO-muAR9.6 (210 ± 11.7 μCi; 7.8 ± 0.4 MBq; 24 μg) at 6, 10, and 16 weeks after inoculation, and the images were collected 6 days after each administration of the radioimmunoconjugate. C, Cryosections of tumor tissue resected from three human patients with HGSOC showing strong immunoreactive staining with muAR9.6 relative to an isotype control IgG used for IHC. D, PET images of female NSG mice bearing three different types of subcutaneous PDX (T; n = 3 mice per PDX) injected with 1.3 mg/kg [⁸⁹Zr]Zr-DFO-muAR9.6 (248 ± 5.3 μCi; 9.2 ± 0.2 MBq; 33.0 ± 4.3 μg). E,Ex vivo biodistribution data collected 6 days after 0.12 ± 0.01 mg/kg (22.7 ± 1.2 μCi; 0.84 ± 0.04 MBq; 3.0 ± 0.3 μg) [⁸⁹Zr]Zr-DFO-muAR9.6 was administered intravenously to mice bearing three types of subcutaneous PDX (n = 4 mice per PDX). Detailed %ID/g values are provided in Supplementary Table S5. The maximum intensity projections have been scaled from 0% to 100%.