RT Journal Article SR Electronic T1 Preparation, Biological Evaluation, and Pharmacokinetics of the Human Anti-HER1 Monoclonal Antibody Panitumumab Labeled with 86Y for Quantitative PET of Carcinoma JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 942 OP 950 DO 10.2967/jnumed.109.071290 VO 51 IS 6 A1 Tapan K. Nayak A1 Kayhan Garmestani A1 Kwamena E. Baidoo A1 Diane E. Milenic A1 Martin W. Brechbiel YR 2010 UL http://jnm.snmjournals.org/content/51/6/942.abstract AB Panitumumab, a human monoclonal antibody that binds to the epidermal growth factor receptor (HER1), was approved by the Food and Drug Administration in 2006 for the treatment of patients with HER1-expressing carcinoma. In this article, we describe the preclinical development of 86Y-CHX-A″-diethylenetriaminepentaacetic acid (DTPA)-panitumumab for quantitative PET of HER1-expressing carcinoma. Panitumumab was conjugated to CHX-A″-DTPA and radiolabeled with 86Y. In vivo biodistribution, PET, blood clearance, area under the curve, area under the moment curve, and mean residence time were determined for mice bearing HER1-expressing human colorectal (LS-174T), prostate (PC-3), and epidermoid (A431) tumor xenografts. Receptor specificity was demonstrated by coinjection of 0.1 mg of panitumumab with the radioimmunoconjugate. Results: 86Y-CHX-A″-DTPA-panitumumab was routinely prepared with a specific activity exceeding 2 GBq/mg. Biodistribution and PET studies demonstrated a high HER1-specific tumor uptake of the radioimmunoconjugate. In mice bearing LS-174T, PC-3, or A431 tumors, the tumor uptake at 3 d was 34.6 ± 5.9, 22.1 ± 1.9, and 22.7 ± 1.7 percentage injected dose per gram (%ID/g), respectively. The corresponding tumor uptake in mice coinjected with 0.1 mg of panitumumab was 9.3 ± 1.5, 8.8 ± 0.9, and 10.0 ± 1.3 %ID/g, respectively, at the same time point, demonstrating specific blockage of the receptor. Normal organ and tumor uptake quantified by PET was closely related (r2 = 0.95) to values determined by biodistribution studies. The LS-174T tumor had the highest area under the curve (96.8 ± 5.6 %ID·d·g−1) and area under the moment curve (262.5 ± 14.9 %ID·d2·g−1); however, the tumor mean residence times were identical for all 3 tumors (2.7–2.8 d). Conclusion: This study demonstrates the potential of 86Y-CHX-A″-DTPA-panitumumab for quantitative noninvasive PET of HER1-expressing tumors and represents the first step toward clinical translation.