Matthew M Niemeyer, Yifan Wang, Maximillian J Carlino, Lobna Elkhadragy, Odile David, Luke R Jordan, Andrew J Lipnik, Daniel Blanco, Vera Mehta, Evelyn Sambora, Lawrence B Schook, Ketan Y Shah, Russell O Simpson, Ron C Gaba, Kyle M Schachtschneider
{"title":"大聚集白蛋白（MAA）在猪肺癌模型形成后的生物分布及其特性。","authors":"Matthew M Niemeyer, Yifan Wang, Maximillian J Carlino, Lobna Elkhadragy, Odile David, Luke R Jordan, Andrew J Lipnik, Daniel Blanco, Vera Mehta, Evelyn Sambora, Lawrence B Schook, Ketan Y Shah, Russell O Simpson, Ron C Gaba, Kyle M Schachtschneider","doi":"10.1016/j.jvir.2025.08.007","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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.</p><p><strong>Materials and methods: </strong>Three transgenic Oncopigs harboring Cre-inducible TP53<sup>R167H</sup> and KRAS<sup>G12D</sup> 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 (<sup>99m</sup>Tc) macroaggregated albumin (MAA) infusion from bronchial and pulmonary arteries targeting the same tumor with 7 days between procedures. <sup>99m</sup>Tc MAA biodistribution was quantified and compared using single photon emission computed tomography (SPECT).</p><p><strong>Results: </strong>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 <sup>99m</sup>Tc MAA tumor targeting from bronchial and pulmonary arteries in all 4 tumor-bearing Oncopigs. Mean tumor-to-normal ratio after bronchial arterial <sup>99m</sup>Tc 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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":49962,"journal":{"name":"Journal of Vascular and Interventional Radiology","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biodistribution of Macroaggregated Albumin after Tumor Model Development and Characterization in a Porcine Lung Cancer Model.\",\"authors\":\"Matthew M Niemeyer, Yifan Wang, Maximillian J Carlino, Lobna Elkhadragy, Odile David, Luke R Jordan, Andrew J Lipnik, Daniel Blanco, Vera Mehta, Evelyn Sambora, Lawrence B Schook, Ketan Y Shah, Russell O Simpson, Ron C Gaba, Kyle M Schachtschneider\",\"doi\":\"10.1016/j.jvir.2025.08.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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.</p><p><strong>Materials and methods: </strong>Three transgenic Oncopigs harboring Cre-inducible TP53<sup>R167H</sup> and KRAS<sup>G12D</sup> 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 (<sup>99m</sup>Tc) macroaggregated albumin (MAA) infusion from bronchial and pulmonary arteries targeting the same tumor with 7 days between procedures. <sup>99m</sup>Tc MAA biodistribution was quantified and compared using single photon emission computed tomography (SPECT).</p><p><strong>Results: </strong>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 <sup>99m</sup>Tc MAA tumor targeting from bronchial and pulmonary arteries in all 4 tumor-bearing Oncopigs. Mean tumor-to-normal ratio after bronchial arterial <sup>99m</sup>Tc 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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":49962,\"journal\":{\"name\":\"Journal of Vascular and Interventional Radiology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-08-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Vascular and Interventional Radiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jvir.2025.08.007\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PERIPHERAL VASCULAR DISEASE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Vascular and Interventional Radiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jvir.2025.08.007","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0
摘要
目的：验证携带Cre重组酶（AdCre）的腺病毒载体在Oncopig气管内输注诱导肺肿瘤，并验证支气管动脉钇-90经动脉放射栓塞（TARE）是治疗肺癌的最佳输注途径。材料和方法：通过气管内输注AdCre诱导3个含有cree诱导的TP53R167H和KRASG12D突变的转基因Oncopigs。肿瘤通过2周和4周的计算机断层扫描和病理进行表征。另外5例oncopig进行肿瘤诱导，然后从支气管和肺动脉经动脉输注技术-99m巨聚集白蛋白（Tc-99m MAA），靶向同一肿瘤，手术间隔7天。使用单光子发射计算机断层扫描定量和比较Tc-99m MAA的生物分布。结果：3/3的肿瘤诱导成功。诱导后2周平均肿瘤大小为2.9 x 2.2 cm。病理显示细支气管周围慢性炎症，大肿块炎性细胞病变，KRAS阳性。在另外4/5例oncopig中肿瘤诱导成功，在所有4例荷瘤oncopig中Tc-99m MAA成功靶向支气管和肺动脉肿瘤。支气管动脉输注Tc-99m MAA后平均瘤正常比显著高于肺动脉输注后（8.10±4.30 vs. 2.40±2.15,p=0.032）。食管（0.79±0.80 vs. 0.20±0.16,p=0.20）、心包（8.83±5.34 vs. 5.87±5.15,p=0.43）、脊髓（0.08±0.09 vs. 0.08±0.08,p=1.0）血管床间活动较低，差异无统计学意义。肾和脑分流的百分比可以忽略不计。结论：肺癌可能在Oncopig中产生，并可用于表征经动脉靶向后的生物分布。支气管动脉TARE应优先考虑较高的肿瘤与正常生物分布。
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.
期刊介绍：
JVIR, published continuously since 1990, is an international, monthly peer-reviewed interventional radiology journal. As the official journal of the Society of Interventional Radiology, JVIR is the peer-reviewed journal of choice for interventional radiologists, radiologists, cardiologists, vascular surgeons, neurosurgeons, and other clinicians who seek current and reliable information on every aspect of vascular and interventional radiology. Each issue of JVIR covers critical and cutting-edge medical minimally invasive, clinical, basic research, radiological, pathological, and socioeconomic issues of importance to the field.
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