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- W1943940215 abstract "139 Objectives Blocking tumor angiogenesis by VEGF inhibition showed clinical benefit, however this effect is transient indicating the need for more effective antiangiogenic strategies. RO5323441 is a novel antibody against placental growth factor (PlGF; a pro-angiogenic VEGF homolog produced by many tumors) and has antitumor activity in preclinical models of cancer. This study aims at development and preclinical validation of 89Zr-RO5323441 for visualization of PlGF expression and whole body distribution of RO5323441. Methods 89Zr-RO5323441 was analyzed in vitro for (radiochemical) purity, stability and immunoreactivity. 89Zr-RO5323441 tumor uptake and organ distribution was assessed with µPET imaging and ex vivo biodistribution analysis at 3 protein doses (10, 50 and 500 µg), and compared with 111In-IgG at 24, 72 and 144 h post injection. The study was performed in mice bearing a human hepatocellular carcinoma Huh7 xenograft. Results 89Zr-RO5323441 was produced with high specific activity (up to 1 GBq 89Zr/mg RO5323441), a radiochemical purity >95%, stability in human serum at 37 0C during >1 week and a fully preserved immunoreactivity. μPET quantification of 89Zr-RO5323441 tumor uptake showed good correlation (R2 = 0.85) with ex vivo biodistribution analysis. Ex vivo tumor uptake of 10, 50 and 500 µg 89Zr-RO5323441 at 144 h was 10.3 ± 3.0, 7.1 ± 0.5 and 5.3 ± 0.6 %ID/g, respectively. All 3 doses of 89Zr-RO5323441 showed a higher tumor uptake at 144 h compared to 111In-IgG of +109 % (P = .0234), +91 % (P = .0041) and +79 % (P = .0004) for 10, 50 and 500 µg, respectively. Tumor uptake of 10 µg 89Zr-RO5323441 at 24, 72 and 144 h was 5.2 ± 1.3, 8.0 ± 1.8 and 10.3 ± 3.0 %ID/g, respectively. Conclusions 89Zr-RO5323441 was produced with clinical grade qualifications and 89Zr-RO5323441 µPET imaging showed time and dose dependent specific tumor uptake. 89Zr-RO5323441 is now ready for further preclinical, as well as clinical, evaluation. Research Support Roche, ESMO and Dutch Cancer Society" @default.
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- W1943940215 date "2011-05-01" @default.
- W1943940215 modified "2023-09-27" @default.
- W1943940215 title "PlGF-PET with 89Zr-RO5323441: Dose escalation study in human tumor xenografts" @default.
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