title: Breast cancer metastasis to bone: evaluation of bioluminescent imaging and microSPECT/CT for detecting bone metastasis in immunodeficient mice.
abstract: This study sought to determine if weekly X-ray exposure affected breast cancer cell metastasis to bone and to also evaluate the use of bioluminescent imaging (BLI) and microSPECT for detection of metastatic bone lesions. Five week old nude mice were randomly assigned to the CT exposed (n = 7) and no CT exposure (n = 6) treatment groups. Mice received an intracardiac injection of MDA-MB-435 human breast cancer cells transduced with luciferase, or a sham injection (saline). The CT exposed group of mice received CT irradiation once a week for 5 weeks. All mice underwent weekly BLI and select mice received Tc-99m-MDP followed by microSPECT imaging after 5 weeks. Pathological evaluation and histomorphometry were used to assess the affect of CT X-rays on bone metastasis and to evaluate BLI. BLI results found no significant difference in metastasis between animals that received CT and those that did not (P > 0.05); however, histomorphometry of the knee joints revealed a significant increase (P = 0.029) in tumor area of the leg bones in mice that received CT exposure (60% +/- 7%) compared to animals that did not receive CT scans (33% +/- 8%). Compared to histological analysis, BLI of the leg and spine was determined to have excellent sensitivity (100%), good specificity (80-90%) and accuracy (90-96%), a positive predictive value of 81-93% and a 100% negative predictive value. Thus, multi-modality imaging techniques can be very useful for monitoring bone metastasis, however microCT X-rays should be used judiciously in order to limit irradiation that may stimulate increased metastasis to specific regions of the skeleton. MicroSPECT imaging did not detect metastatic lesions in the legs of these young nude mice.
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, 701 South 19th Street, LHRB Room 531, Birmingham, Alabama 35294, USA.
authors.forename: S
authors.initials: S
authors.lastname: Cowey
authors.forename: A A
authors.initials: AA
authors.lastname: Szafran
authors.forename: J
authors.initials: J
authors.lastname: Kappes
authors.forename: K R
authors.initials: KR
authors.lastname: Zinn
authors.forename: G P
authors.initials: GP
authors.lastname: Siegal
authors.forename: R A
authors.initials: RA
authors.lastname: Desmond
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Evans
authors.forename: R W
authors.initials: RW
authors.lastname: Hardy
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary; D001842:Bone and Bones / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D049449:Luminescence; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D011237:Predictive Value of Tests; D011897:Random Allocation; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000009:adverse effects / Q000379:methods; D014183:Transplantation, Heterologous