European Association of Nuclear Medicine October 20-23, 2021 Virtual

Aim/Introduction: Over the last decades, the use of 18F-FDG has taken a pivotal role in oncological diagnosis, staging and follow-up. While endless research has shown the clinical importance of 18F-FDG, we remain unaware how 18F-FDG behaves in and around human malignancies on a submillimetric scale. Unfortunately, as glucose metabolism is an active process, pathological assessment of relevant protein markers was found to be inadequate in correctly predicting 18F-FDG-uptake. Technological improvements are resulting in increasing spatial resolution for PET-scanners, therefore an urgent understanding of 18F-FDG-distribution on these higher resolutions is required. Materials and Methods: In the current study, we developed a methodology that enabled direct coregistration of the radioactivity-distribution in a surgically resected specimen with histopathological assessment. Patients were injected with 4 MBq/kg of 18F-FDG prior to the initiation of standard of care surgical oncological resection. After resection of the malignancy, the surgical specimen was imaged using preclinical micro-PET and -CT devices with a spatial resolution of 800µm and 50µm, respectively. After imaging, the specimen was freshly sliced into thin slices of approximately 2mm by a pathologist. One slice was snap-frozen and frozen sections were imaged using an autoradiographic flm overnight. Following the imaging, frozen sections were stained with standard hematoxylin and eosin staining. Pathological results were overlayed with the results of 18F-FDG PET/CT and autoradiography to coregister the histopathological and imaging results. Results: We performed this methodology on a total of four patients with cutaneous squamous cell carcinoma (n=2), angiosarcoma (n=1) and thyroid medullary carcinoma (n=1). While the mean time between injection and autoradiography was 3h49, we were able to image sufcient radioactivity to directly coregister the results with the clinical pathological frozen sections. All regions with identifed malignant tissue displayed increased 18F-FDG-uptake. However, uptake was not limited to these regions, as a similar increased uptake was identifed in adjacent benign sebaceous glands. Interestingly, we also identifed a heterogeneous 18F-FDGuptake in separate clusters of malignant tissue, which could partly be explained by the cluster’s amount of peritumoral infammatory cells. Conclusion: To the best of our knowledge, these results are the frst to describe direct coregistration of 18F-FDG with the gold standard of histopathology in any human malignancy. These heterogeneous results display an important diversity in metabolic activity between diferent tumor and peritumoral tissues. The use of this methodology could increase our understanding of radiotracer distribution in human diseases on a previously unprecedented scale in clinical nuclear medicine.