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Biodistribution of Macroaggregated Albumin after Tumor Model Development and Characterization in a Porcine Lung
Matthew M Niemeyer1, Yifan Wang2, Maximillian J Carlino3
1Section of Interventional Radiology, Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
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.
