Mammary Cancer Bone Metastasis Follow-up Using Multimodal Small-Animal MR and PET Imaging

Abstract

Despite tremendous progress in the management of breast cancer, the survival rate of this disease is still correlated with the development of metastases-most notably, those of the bone. Diagnosis of bone metastasis requires a combination of multiple imaging modalities. MR imaging remains the best modality for soft-tissue visualization, allowing for the distinction between benign and malignant lesions in many cases. On the other hand, PET imaging is frequently more specific at detecting bone metastasis by measuring the accumulation of radiotracers, such as 18 F-sodium fluoride ( 18 F-NaF) and 18 F-FDG. Thus, the main purpose of this study was to longitudinally monitor bone tumor progression using PET/MR image coregistration to improve noninvasive imaging-assisted diagnoses. Methods: After surgical implantation of mammary MRMT-1 cells in a rat femur, we performed minimally invasive imaging procedures at different time points throughout tumor development. The procedure consisted of sequential coregistered MR and PET image acquisition, using gadolinium-diethylenetriaminepentaacetic acid (DTPA) as a contrast agent for MR imaging and 18 F-FDG, 11 C-methionine, and 18 F-NaF as molecular tracers for PET imaging. The animals were then euthanized, and complementary radiologic (micro-CT scans) and histologic analyses were performed. Results: In this preclinical study, we demonstrated that coregistered MR and PET images provide helpful information in a rat mammary-derived bone cancer model. First, MR imaging provided a high-definition anatomic resolution that made the localization of bone resorption and tumor extension detectable between days 9 and 18 after the injection of cancer cells in the medullary channel of the femur. Indeed, the calculation of mean standardized uptake value (SUV mean ) and maximal SUV (SUV max ) in bone and softtissue regions, as defined from the gadolinium-DTPA contrastenhanced MR images, showed 18 F-NaF uptake modifications and increased 18 F-FDG or 11 C-methionine uptake in the bone and surrounding soft tissues. 18 F-FDG and 11 C-methionine were compared in terms of the magnitude of change in their uptake and variability. We observed that 11 C-methionine SUV mean variations in the tumor were more important than those of 18 F-FDG. We also found fewer interindividual variations using SUV mean as a quantitative parameter than SUV max . Conclusion: This preclinical evaluation demonstrated that a PET/MR image coregistration protocol provided a powerful tool to evaluate bone tumor progression in a rat model of bone metastasis and that this protocol could be translated to improve the clinical outcome for metastatic breast cancer management.

A novel mouse model of human prostate cancer to study intraprostatic tumor growth and the development of lymph node metastases

“…Though we did not observe metastases in organs other than the iliacal lymph nodes, the detection of such in all abdominal organs as well as the bone, and the lungs should be possible. [36][37][38] However, it enables an excellent visualization of the skeletal system and might therefore be the most appropriate imaging technique to detect bone metastases 39 though we did not observe such in our study. Besides that, lung metastases can be reliable detected by in vivo micro-CT. 40 One alternative technique frequently used to monitor tumor growth in orthotopic xenograft models of PCa is bioluminescence, 41,42 which is easy to use but comes along with some serious constraints:…”

“…9.4T small animal MRI allowed an excellent delineation of prostate tumors as well as lymph node metastases in T2‐weighted sequences. Though we did not observe metastases in organs other than the iliacal lymph nodes, the detection of such in all abdominal organs as well as the bone, and the lungs should be possible . While the soft tissue contrast of this technique is much better than that of ultrasonography, its resolution is worse (100 μm vs 33 μm).…”

Animal Models of Bone Metastasis

“…When injected intraosseously into Sprague-Dawley rats, osteolytic or mixed osteolytic/osteoblastic metastases developed. 25,79 …”

Multimodal imaging analysis of an orthotopic head and neck cancer mouse model and application of anti‐CD137 tumor immune therapy

“…Correlatively, CT or MRI is useful to improve anatomic orientation and to precisely assess the tumor's circumference. CT is preferred for structural bone imaging, whereas MRI displays a better resolution than CT for soft tissues . Multimodal FDG‐PET‐involving imaging has, to the best of our knowledge, never been applied before to an orthotopic head and neck cancer mouse model.…”