Direct co-registration of [F]FDG uptake and histopathology in surgically excised malignancies of the head and neck: a feasibility study.

Purpose: Recent technical advancements in PET imaging have improved sensitivity and spatial resolution. Consequently, clinical nuclear medicine will be confronted with PET images on a previously unfamiliar resolution. To better understand [F]FDG distribution at submillimetric scale, a direct correlation of radionuclide-imaging and histopathology is required.

Methods: A total of five patients diagnosed with a malignancy of the head and neck were injected with a clinical activity of [F]FDG before undergoing surgical resection. The resected specimen was imaged using a preclinical high-resolution PET/CT, followed by slicing of the specimen. Multiple slices were rescanned using a micro-PET/CT device, and one of the slices was snap-frozen for frozen sections. Frozen sections were placed on an autoradiographic film, followed by haematoxylin and eosin staining to prepare them for histopathological assessment. The results from both autoradiography and histopathology were co-registered using an iterative co-registration algorithm, and regions of interest were identified to study radiotracer uptake.

Results: The co-registration between the autoradiographs and their corresponding histopathology was successful in all specimens. The use of this novel methodology allowed direct comparison of autoradiography and histopathology and enabled the visualisation of uncharted heterogeneity in [F]FDG uptake in both benign and malignant tissue.

Conclusion: We here describe a novel methodology enabling the direct co-registration of [F]FDG autoradiography with the gold standard of histopathology in human malignant tissue. The future use of the current methodology could further increase our understanding of the distribution of radionuclides in surgically excised malignancies and hence, improve the integration of pathology and molecular imaging in a multiscale perspective.

Trial Registration: ClinicalTrials.gov Identifier: NCT05068687.