High resolution computed tomography and MRI for monitoring lung tumor growth in mice undergoing radioimmunotherapy: Correlation with histology

A model lung tumor system has been developed in mice for the evaluation of vascular targeted radioimmunotherapy. In this model, EMT-6 mammary carcinom a tumors growing in the lung are treated with Bi-213, an alpha particle emi tter, which is targeted to lung blood vessels using a monoclonal antibody. Smaller tumors (< 100 mu m in diameter) are cured, but larger tumors underg o a period of regression and then regrow and ultimately prove lethal. The g oal of this work was to determine if external imaging with MRI or CT could be used routinely to monitor the growth/regression of lung tumors in live m ice. To attempt to evaluate individual tumors in vivo, animals were initial ly imaged with magnetic resonance imaging (MRI). High resolution MRI images could be obtained only after sacrifice when lungs were not moving. In cont rast, high resolution computed tomography (CT) produced evaluable images fr om anesthetized animals. Serial CT images (up to 5/animal) were collected o ver a 17 day period of tumor growth and treatment. When tumored animals bec ame moribund, animals were sacrificed and lungs were inflated with fixative , embedded in paraffin, and then sectioned serially to compare the detectio n of tumors by high resolution CT with detection by histology. CT proved mo st useful in detecting lung tumors located in the hilar area and least usef ul in detecting serosal surface and anterior lobe tumor foci. Overall, CT i mages of live animals revealed tumors in similar to 2/3 of cases detected i n histologic serial sections when relatively few tumors were present per lu ng. Detection of lesions and their resolution post therapy were complicated due to residual hemorrhagic, regressing tumor nodules and the development of lung edema both of which appeared as high density areas in the CT scans. We conclude that the microCT method used could identify some lung tumors a s small as 100 mu m in diameter; however, no concrete evaluation of therapy induced regression of the tumors could be made with CT analyses alone. (C) 2000 American Association of Physicists in Medicine. [S0094-2405(00)02505- 0].