Biodistribution of Macroaggregated Albumin (MAA) After Tumor Model Development and Characterization in a Porcine Lung Cancer Model.

Purpose: Demonstrate intra-tracheal infusion of an adenoviral vector carrying Cre recombinase (AdCre) induces lung tumors in the Oncopig, and verify bronchial arterial yttrium-90 transarterial radioembolization (TARE) as the optimal infusion route for lung cancer.

Materials And Methods: Three transgenic Oncopigs harboring Cre-inducible TP53 and KRAS mutations underwent tumor induction via intra-tracheal AdCre infusion. Tumors were characterized with 2- and 4-week computed tomography and pathology. Five additional Oncopigs underwent tumor induction followed by transarterial technetium-99m macroaggregated albumin (Tc-99m MAA) infusion from bronchial and pulmonary arteries targeting the same tumor with 7 days between procedures. Tc-99m MAA biodistribution was quantified and compared using single-photon emission computed tomography.

Results: Tumor induction was successful in 3/3 Oncopigs. Mean tumor size 2-weeks post-induction was 2.9 x 2.2 cm. Pathology revealed peribronchiolar chronic inflammation, large mass-forming inflammatory cell lesions, and KRAS positivity. Tumor induction was successful in 4/5 additional Oncopigs, with successful Tc-99m MAA tumor targeting from bronchial and pulmonary arteries in all 4 tumor-bearing Oncopigs. Mean tumor-to-normal ratio after bronchial arterial Tc-99m MAA infusion was significantly higher than after pulmonary arterial infusion (8.10±4.30 vs. 2.40±2.15, p=0.032). Esophageal (0.79±0.80 vs. 0.20±0.16, p=0.20), pericardial (8.83±5.34 vs. 5.87±5.15, p=0.43), and spinal cord (0.08±0.09 vs. 0.08±0.08, p=1.0) activities were low and not statistically different between vascular beds. Renal and brain shunt percentages were negligible.

Conclusion: Lung cancer may be generated in the Oncopig, and may be used to characterize biodistribution after transarterial targeting. Bronchial arterial TARE should be prioritized based on higher tumor-to-normal biodistribution.