PT  - JOURNAL ARTICLE
AU  - Thijs H. Oude Munnink
AU  - Karin R. Tamas
AU  - Marjolijn N. Lub-de Hooge
AU  - Silke R. Vedelaar
AU  - Hetty Timmer-Bosscha
AU  - Annemiek M.E. Walenkamp
AU  - K. Michael Weidner
AU  - Frank Herting
AU  - Jean Tessier
AU  - Elisabeth G.E. de Vries
TI  - Placental Growth Factor (PlGF)–Specific Uptake in Tumor Microenvironment of <sup>89</sup>Zr-Labeled PlGF Antibody RO5323441
AID  - 10.2967/jnumed.112.112086
DP  - 2013 Jun 01
TA  - Journal of Nuclear Medicine
PG  - 929--935
VI  - 54
IP  - 6
4099  - http://jnm.snmjournals.org/content/54/6/929.short
4100  - http://jnm.snmjournals.org/content/54/6/929.full
SO  - J Nucl Med2013 Jun 01; 54
AB  - Placental growth factor (PlGF) is a member of the proangiogenic vascular endothelial growth factor family, which is upregulated in many tumors. RO5323441, a humanized monoclonal antibody against PlGF, showed antitumor activity in human tumor xenografts. We therefore aimed to radiolabel RO5323441 and preclinically validate this tracer to study drug tumor uptake and organ distribution by PET imaging. 89Zr-RO5323441 was tested for stability and immunoreactivity in vitro. Methods: The tumor uptake and organ distribution for 10, 50, and 500 μg of 89Zr-RO5323441 was assessed in mice bearing human PlGF–expressing hepatocellular cancer (Huh7) xenografts or human renal cell carcinoma (ACHN) xenografts without detectable human PlGF expression. The effect of pretreatment with RO5323441 (20 mg/kg) on 89Zr-RO5323441 tumor uptake was analyzed in Huh7 xenografts. 111In-IgG served as a control for nonspecific tumor uptake and organ distribution. Cy5-RO5323441 was injected to study the intratumor distribution of RO5323441 with fluorescence microscopy. Results: 89Zr-RO5323441 showed a time- and dose-dependent tumor accumulation. Uptake in Huh7 xenografts at 10 μg of 89Zr-RO5323441 was 8.2% ± 1.7% injected dose (ID)/cm3 at 144 h after injection, and in ACHN xenografts it was 5.5 ± 0.3 %ID/cm3 (P = 0.03). RO5323441 pretreatment of Huh7 xenograft–bearing mice reduced 89Zr-RO5323441 tumor uptake to the level of nonspecific 111In-IgG uptake. Cy5-RO5323441 was present in the tumors mainly in the microenvironment. Conclusion: The findings show that RO5323441 tumor uptake is PlGF-specific and time- and dose-dependent.