Abstract P4-01-19: Enhanced sensitivity to detect metastases of breast cancer to the lung and monitor response to inhibition of metastasis by IGF1R inhibitor using SWIFT MRI
Authors: Sachdev D , Idiyatullin D , Corum C , Weber J , Garwood M , Kobayashi N 
Published: August 2014

Breast cancers metastasize to the bone, lung, brain and liver and mortality from breast cancer is due to metastases. Drugs that inhibit metastasis in particular of triple negative (TN) breast cancers, more sensitive methods to image metastases and imaging biomarkers to monitor response to these drugs at sites of metastasis are needed to reduce mortality. The type I insulin-like growth factor receptor (IGF1R) regulates metastasis and drugs targeting IGF1R and or insulin receptor inhibit metastasis of TN breast cancer cells in mouse models. The initial clinical trials of these drugs have not been very successful and point to the need to develop imaging biomarkers for this therapy. While MRI is a powerful tool for detecting and imaging cancer, its utility in imaging metastasis to the lung is limited due to the challenges of lung MRI with conventional 3D gradient echo (GRE). MRI does not visualize lung well, mainly due to the abundance of air-tissue interfaces, which cause the MR signal to decay too rapidly for conventional MRI pulse sequences to capture. Clinically lung metastases are monitored by CT or PET but exposure of patients to ionizing radiation is a concern and problematic in longitudinal studies monitoring response to a targeted drug. Further MRI can also be useful in measuring metabolite levels using MR spectroscopy (MRS). Therefore, we evaluated the capability of a novel MR sequence called sweep imaging with Fourier transformation (SWIFT), where the data is acquired concurrently with the radiofrequency pulse, to detect breast cancer metastases to lung and test if inhibition of metastases by an IGF1R targeted drug can be monitored by SWIFT. We used the tail vein injection model of breast cancer metastasis with MDA-MB-231-LM2, a lung-seeking metastatic TN breast cancer cell line. Lung metastases were monitored with bioluminescence imaging (BLI) and MRI every week. MRI was done with two pulse sequences: SWIFT (with a short echo time or TE∼3 μs) and GRE (with a longer TE = 2.2 ms). SWIFT showed significantly higher sensitivity in detecting signals from lung parenchyma compared to GRE and structural information was visible in the area of the lungs. Metastatic tumor growth in the lung induced a progressive increase in signal from the lung parenchyma in SWIFT images. MIP images from SWIFT clearly visualized the lung vascular structures and their disruption due to progression of breast cancer metastasis. To test if SWIFT can also be useful in monitoring inhibition of metastases, mice injected with cells were treated with either vehicle or an IGF1R inhibitor (huEM164) twice a week. When inhibition of metastases in the huEM164 treated group compared to the vehicle group was evident by BLI, MR images were acquired. SWIFT was sensitive in detecting the inhibition of metastases by the IGF1R antibody. Our data show that high sensitivity to fast-decaying signals and tolerance to the magnetic susceptibility in SWIFT enhance the capability to detect signal and structural changes in the lung parenchyma and vasculature due to metastasis of breast cancer. Further, SWIFT was also sensitive to monitor inhibition of metastasis in response to IGF1R targeted drugs.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-19.