PT - JOURNAL ARTICLE AU - Sibaprasad Bhattacharyya AU - Ling Wei AU - Lisa Riffle AU - G. Hill AU - Paula Jacobs AU - James Tatum AU - James Doroshow AU - Joseph Kalen TI - Preclinical evaluation of 89Zr-labeled panitumumab as a potential PET probe for HER1-expressing carcinomas DP - 2012 May 01 TA - Journal of Nuclear Medicine PG - 1693--1693 VI - 53 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/53/supplement_1/1693.short 4100 - http://jnm.snmjournals.org/content/53/supplement_1/1693.full SO - J Nucl Med2012 May 01; 53 AB - 1693 Objectives Anti-HER1 monoclonal antibody (mAb), panitumumab (Victibix®) is a fully humanized mAb recently (2006) approved by the FDA for the treatment of epidermal growth factor receptor (EGFR, HER1)-expressing colorectal cancers. Currently, it is being evaluated in patients with other types of HER1-expressing cancers, such as breast, lung, head and neck, renal, and ovarian. We anticipated that 89Zr labeled panitumumab would be an ideal imaging probe to quantify EGFR (HER1)-expression to guide therapy and dosing. Methods At first, panitumumab was chemically conjugated with bifunctional chelate desferrioxamine (DFO) at well defined ratios (1:1-2) and subsequently labeled with 89Zr. Biodistribution studies were performed (1.85 MBq; I.V. tail-vein injected) on non-tumor bearing athymic nude (male and female) mice. Athymic nude xenograft tumor bearing mice with very low (BT-474), medium (MDA-MB-231), and high (MDA-MB-468) HER1-expression levels were administered 89Zr-DFO-panitumumab formulations (10.18±1.24 MBq, 50-60 µg of mAb in 200 µL of 0.9% saline) via tail-vein injection. Animal imaging experiments were conducted on a micro-PET/CT scanner at 24, 48, 72, 96, and 144 hours post injection. Results After a PD10 column purification the radiochemical yield and purity of 89Zr-Panitumumab was > 80% and > 98% respectively (n=10). Biodistribution study resulted in minimal (1-4 %ID/gm) organ uptake for the majority of organs. Immuno-PET images of 89Zr-DFO-panitumumab recorded in different mice xenograft models showed a good correlation (Fig.1) between HER1-expression level and tumor uptake. Conclusions 89Zr-DFO-panitumumab has been prepared with high radiochemical purity and specific activity. Immuno-PET experiments indicated that 89Zr-DFO-panitumumab shows excellent potential as a PET tracer for specific noninvasive delineation of HER1 positive tumors in vivo. Research Support Funded by NCI/NIH, Contract No. HHSN261200800001E