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Introduction: Patients (pts) with borderline resectable (BR) pancreatic cancer (PC) derive a clear survival benefit when margin-negative resection can be achieved after neoadjuvant treatment (tx). As such, reliable imaging is desperately needed to identify those patients with the best chance of surgical benefit. Current imaging with CT/MRI and standard 18F-fludeoxyglucose (FDG) PET lacks sensitivity and specificity to resolve residual tumor contact with the large blood vessels of the vascular groove. Dynamic PET with kernel-based image reconstruction developed by our group has potential to overcome limits of standard static PET by robust parametric imaging of radiotracer kinetics. KBD FDG-PET provides the FDG kinetic parameter K1 for tumor perfusion and Ki for tumor glucose utilization. A lower Ki/K1 ratio indicates a better perfused, less metabolically active tumor and is derived by our method without need for separate perfusion CT/MRI. Methods: Pts with PC staged as BR as defined by consensus guidelines were eligible. Pts were assessed by CA 19-9 and CT/MRI along with KBD FDG-PET both pre-tx and post-tx. KBD FDG PET was performed by IV bolus of 10 mCi of FDG followed by 60-min PET data acquisition. A 3-compartment model with 5 micro kinetic parameters K1, k2, k3, k4, and fv was used where K1 (mL/min/mL) denotes the rate constant of FDG transport from plasma to tissue, k2 (1/min) the transport rate from tissue to plasma, k3 (1/min) the rate of FDG conversion to FDG 6-phosphate, k4 (1/min) the rate of dephosphorylation, and fv the fractional blood volume. Ki was calculated from micro parameters by the formula K1*k3/(k2+k3). Parametric images of these kinetic parameters were obtained by voxel-wise implementation of kinetic modeling. Results: 4 pts were enrolled, 3 pts had pre- and post-tx KBD FDG-PET, and 2 pts were resected. In the 3 evaluable pts, an overall 62% decrease in tumor glucose utilization was observed (mean pre-tx Ki=.03, [range .013-.045]; mean post-tx Ki=.011 [range .004-.016]. Mean pre-tx K1=.37 (range .26-.50) and mean post-tx K1=.38 (range .31-.46). Delta Ki was -17%, -47%, and -91% and delta Ki/K1 was -9%, -28%, and -95% in pts 1, 2, 3 respectively. Pt 3 had the highest pre-tx Ki and the lowest pre-tx K1, but had a >90% decrease in Ki and Ki/K1 post-tx, indicating a significant decrease in metabolic activity and concomitant increase in perfusion. Despite persistent superior mesenteric vein (SMV) abutment on standard post-tx imaging, margin-negative resection was achieved. In contrast, pt 1 had the lowest pre-tx Ki and highest pre-tx K1, but had a Citation Format: John P. Schwerkoske, Guobao Wang, Kit W. Tam, Jasmine C. Huynh, Heather H. Hunt, Michael L. Rusnak, Cameron C. Foster, Michael T. Corwin, Karen E. Matsukuma, Dorina Gui, May T. Cho, Richard J. Bold, Ramsey D. Badawi, Edward J. Kim. Pilot study of kernel-based dynamic (KBD) FDG-PET in patients with borderline resectable pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3045.