Murine biodistribution and human dosimetry estimates of 111In DTPA- and 89Zr DFO-panitumumab

JOURNAL OF NUCLEAR MEDICINE(2012)

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摘要
1513 Objectives Overexpression of the epidermal growth factor receptor (EGFR) is associated with disease progression and treatment resistance. The humanized antibody panitumumab (Victibix) is being used clinically to treat EGFR over-expressing tumors. By radiolabeling panitumumab it may be possible to non-invasively identify which patients may benefit from anti-EGFR therapy and measure the amount of over-expression using SPECT or PET. Methods Panitumumab was labeled with 89Zr through desferrioxamine (DFO) chelator and with 111In through DTPA chelator resulting in a very high radiochemical yield (>80%) and purity (>98%). The radiolabeled compound was IV tail-vein injected into athymic nude mouse cohorts sacrificed at daily intervals over 6 days to provide biodistribution data from which preliminary human radiation dose estimates were made for PET and SPECT imaging, respectively. Results The biodistributions of 111In and 89Zr were similar (correlation coefficient >0.9 at most time points). Minimal radiotracer was excreted from the body over the entire 6 day period. The resultant radiation dose estimates for 89Zr and 111In are presented below. Conclusions The majority of either radiotracer remained in the blood pool, consistent with panitumumab’s half-life of 7.5 days. Human dosimetry studies using either 1.4 mCi of 89Zr or 4.3mCi of 111In will keep the radiation dose estimates within conservative limits ( Research Support NCI/NI
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human dosimetry estimates,murine,dfo-panitumumab
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