Biodistribution of Macroaggregated Albumin after Tumor Model Development and Characterization in a Porcine Lung Cancer Model.

PURPOSE: To demonstrate that intratracheal infusion of an adenoviral vector carrying Cre recombinase (AdCre) induces lung tumors in the Oncopig and verify that bronchial arterial yttrium-90 transarterial radioembolization (TARE) is the optimal infusion route for lung cancer.

MATERIALS AND

METHODS

Three transgenic Oncopigs harboring Cre-inducible TP53R167H and KRASG12D mutations underwent tumor induction via intratracheal AdCre infusion. Tumors were characterized with 2- and 4-week computed tomography (CT) and pathology. Five additional Oncopigs underwent tumor induction followed by transarterial technetium-99m (99mTc) macroaggregated albumin (MAA) infusion from bronchial and pulmonary arteries targeting the same tumor with 7 days between procedures. 99mTc MAA biodistribution was quantified and compared using single photon emission computed tomography (SPECT).

RESULTS

Tumor induction was successful in all 3 Oncopigs. Mean tumor size 2 weeks after induction was 2.9 cm × 2.2 cm. Pathology revealed peribronchiolar chronic inflammation, large mass-forming inflammatory cell lesions, and KRAS positivity. Tumor induction was successful in 4 of 5 additional Oncopigs, with successful 99mTc MAA tumor targeting from bronchial and pulmonary arteries in all 4 tumor-bearing Oncopigs. Mean tumor-to-normal ratio after bronchial arterial 99mTc MAA infusion was significantly higher than that after pulmonary arterial infusion (8.10 [SD ± 4.30] vs 2.40 [SD ± 2.15]; P = .032). Esophageal (0.79 [SD ± 0.80] vs 0.20 [SD ± 0.16]; P = .20), pericardial (8.83 [SD ± 5.34] vs 5.87 [SD ± 5.15]; P = .43), and spinal cord (0.08 [SD ± 0.09] vs 0.08 [SD ± 0.08]; P = 1.0) activities were low and not statistically different between vascular beds. Renal and brain shunt percentages were negligible.

CONCLUSIONS

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