TDK conference 2024

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin in both humans and dogs (CIPF) and belongs to a heterogeneous group of interstitial lung diseases. It has a breed predisposition in dogs, and is predominantly found in middle-aged and elderly West Highland White terriers (WHW terriers), but its genetic background has not yet been identified. The progressive nature of restrictive dyspnoea, the characteristic CT findings (milk-glass opacity, mosaic attenuation, reticular pattern) and the histopathological examination of lung tissue are required for the diagnosis of CIPF.

The aim of our study was to confirm the presence of fibrosis in lung tissue of a living animal using a 68Ga isotope-labelled hydrazide radiopharmaceutical developed for CIPF diagnostic purposes and to qualify the severity of the disease without taking a lung biopsy for histopathological examination. Our assays were aimed at the presence of oxidized collagen and its measurable ratio in total lung volume. Hydrazide molecules are chemically bound (by reversible condensation) to allysine, the end product of the collagen cross-linking enzyme lysyl oxidase. Based on clinical presentation, pathological course and bronchoscopic examination, 3 WHW terriers were selected for the study from the patient material of the Endoscopy Laboratory of the University of Veterinary Medicine. Static PET and CT scans of the patients were obtained with the Mediso AnyScan PET/CT machine of the Institute of Biophysics and Radiobiology, Semmelweis University. PET volume data characterizing the oxidized collagen content of the lungs were analyzed using VivoQuant 1.22 software. The radiopharmaceutical was previously validated in rat experiments.

In all three animals, in contrast to the expected normal lung distribution, a high uptake of hydrazide due to pathological fibrosis was depicted on PET images. The location of the pathological lesions in the lung tissue on CT images corresponded with the areas that were most accumulative on PET images. Consistent with the clinical image, a higher proportion of radiopharmaceutical uptake in lung volumes was detected in animals with more severely impaired lungs and severe symptoms.

Based on the results of our experiment, we can conclude that the tested radiopharmaceuticals were associated with fibrotic lung tumours in all three patients. The measurement of oxidized collagen PET may be useful for the diagnosis of CIPF and may play an important role in monitoring different therapeutic strategies. Thus, further studies in a larger number of cases and a lung biopsy control study will be needed to validate the non-invasive method.