RT Journal Article SR Electronic T1 Translation of CCR2-targeted PET imaging of head and neck cancer JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 348 OP 348 VO 61 IS supplement 1 A1 Luehmann, Hannah A1 Heo, Gyu Seong A1 Detering, Lisa A1 Sultan, Deborah A1 Reichert, David A1 Laforest, Richard A1 Primeau, Tina A1 Li, Shunqiang A1 Chernock, Rebecca A1 Jackson, Ryan A1 Gropler, Robert A1 Dehdashti, Farrokh A1 Liu, Yongjian YR 2020 UL http://jnm.snmjournals.org/content/61/supplement_1/348.abstract AB 348Objectives: Head and neck squamous cell carcinoma (HNSCC) accounts for ca. 4% of malignancy worldwide. Although it is curable in the early stages, the survival rate of patients with advanced cancer has not significantly improved. Hence, the current unmet clinical need is to develop diagnostic tools to detect the disease at the early stages. The previous studies revealed the upregulation of chemokine receptor 2 (CCR2) in HNSCC. In this study, we assessed the performance of CCR2 PET detecting HNSCC in patient-derived xenograft (PDX) mouse models and human tissues and translated this radiotracer in humans. Methods: The novel CCR2-targeted PET tracer, 64Cu-DOTA-ECL1i, was employed for PET imaging. Multiple-time-point PET imaging was performed in HNSCC PDX models in order to assess the correlation between tracer uptake and HNSCC progression. Pathophysiological analysis and autoradiography studies of human HNSCC tissues were carried out to confirm CCR2 upregulation and binding of 64Cu-DOTA-ECL1i to human CCR2. Competitive receptor blocking studies were conducted to verify CCR2 specific binding of the radiotracer. 64Cu-DOTA-ECL1i PET/CT in healthy volunteers demonstrated acceptable radiation dosimetry. PET/CT imaging in head and neck cancer patients is underway. Results: Tumor uptake was gradually increased in HNSCC PDX mice from 0.87 ± 0.14 %ID/g at 9 weeks post tumor implantation to 1.70 ± 0.35 %ID/g at 13 weeks. Competitive receptor blocking showed significantly decreased tumor uptake (p < 0.005), indicating the targeting specificity of the tracer. IHC showed CCR2 overexpression in PDX tumors and human HNSCC tissues. Autoradiography studies demonstrated the binding of 64Cu-DOTA-ECL1i to human CCR2. Human radiation dosimetry in healthy volunteers showed 0.064 ± 0.011 rem/mCi of gender average effective dose (0.07 rem/mCi for females and 0.0575 rem/mCi for males). The dose-limiting organ is the urinary bladder wall due to rapid renal clearance. PET healthy volunteers showed minimal tracer uptake in the head and neck area. Conclusions: CCR2 is a promising imaging biomarker for human HNSCC imaging. The sensitivity and specificity of 64Cu-DOTA-ECL1i warrant further investigation in HNSCC patients.