Baseline 18F fluorodeoxyglucose(FDG)-positron emission tomography (PET) in patient derived (PD) xenograft models from the National Cancer Institute Patient Derived Model Repository (PDMR). (2021)

1470 Objectives: FDG PET is the most widely used metabolic imaging biomarker in oncology. The process driving FDG uptake is the reprogramming of the cancer cell for aerobic glycolysis to support cell growth. The degree of uptake of FDG correlates with tumor differentiation, aggressiveness, and prognosis, but uptake values vary markedly across histologies. This work provides baseline FDG uptake values for a sub-set of PDX models available from the NCI PDMR to assist investigators in selecting models for preclinical and co-clinical investigations using FDG PET as an imaging biomarker.
 Methods: Animal studies were performed according to the Frederick National Laboratory for Cancer Research (Frederick, MD) Institutional Animal Care and Use Committee guidelines. Models were selected for imaging based on researcher interest as reflected in requests for samples, metastatic potential, and rare/recalcitrant cancers. Tumor fragments (8 mm3) were implanted into the right flank of NOD-scid gamma (NSG) mice. When tumors reached adequate size but not exceeding 1 cm in longest dimension the mice were imaged with 2-deoxy-2-(18F)fluoro-D-glucose ([18F]-FDG) positron emission tomography with either X-ray computed tomography or T2w MRI to evaluate photon attenuation (Inveon Multi-Modality PET/CT, Siemens Medical; NanoScan PET/CT, Mediso; and M7-SimPET MRI/PET Aspect). Mice were fasted (allowed water) for 8-12 hours prior to [18F]-FDG injection (6.76 ± 1.25 MBq) via tail-vein injection. PET imaging began at approximately 1-hour post injection. Mice were imaged in the prone position for attenuation correction, followed by a 20-minute PET acquisition (acquisition and reconstruction parameters per vendor recommendations). The animal body temperature (thermostat controlled heated table at 34-37°C) was maintained from the time the animal entered the imaging room, through anesthesia induction, imaging, and until recovery from anesthesia. Isoflurane anesthesia was administered via an induction chamber (3% pre-imaging) and nose cone (1.5-2% during imaging) with oxygen as the carrier gas at a flow of 1 l/min. Pulmonary function was monitored during scanning and the anesthesia (1.5 - 2% Isoflurane) was regulated to maintain a pulmonary rate between 50 and 90 breaths per minute (bpm). [18F]-FDG PET/CT or PET/MRI DICOM images were displayed and fused on a MIM workstation (v 6.6.5, MIM Software Inc, Cleveland, OH). [18F]-FDG uptake was determined using a volume of interest (VOI) defined on CT or MRI, and the maximum standardized uptake value normalized by body weight (SUVbw max) was calculated.
 Results: 72 PDX models in 430 mice were imaged with SUVbw max per model ranging from 0.61 to 10.24. Among these 19 were from metastatic sites, 4 of unknown origin and 2 from blood with the remaining 47 from primary tumor; 28 models were designated rare tumors (Graph). The most common were adenocarcinoma pancreas (8) with SUVbw max from 1.15 to 3.19, adenocarcinoma of colon (7) with SUVbw max ranging from 1.15 to 5.83, urinary bladder (6) with SUVbw max from 1.26 to 6.93 and melanoma (6) with SUVbw max from 1.58 to 3.60. In 19 PDX models at least one repeat imaging with a subsequent passage of the xenograft or a repeat implantation with a new fragment was performed and is included in the data that will be presented.
 Conclusions: PDX models were developed to more closely emulate human cancers and provide a resource for preclinical and co-clinical development of therapies. Imaging is well suited to facilitate this goal and most co-clinical trials will likely involve PET imaging with FDG. Baseline FDG uptake in PDX models available to researchers from the NCI PDMR can assist in selecting models where FDG uptake and modulation may serve as an in vivo biomarker.