title: Detection of breast cancer microcalcification using (99m)Tc-MDP SPECT or Osteosense 750EX FMT imaging.
abstract: BACKGROUND
  In previous work, we demonstrated the presence of hydroxyapetite (type II microcalcification), HAP, in triple negative MDA-MB-231 breast cancer cells. We used (18)F-NaF to detect these types of cancers in mouse models as the free fluorine, (18)F(-), binds to HAP similar to bone uptake. In this work, we investigate other bone targeting agents and techniques including (99m)Tc-MDP SPECT and Osteosense 750EX FMT imaging as alternatives for breast cancer diagnosis via targeting HAP within the tumor microenvironment.
  
  
  METHODS
  Thirteen mice were injected subcutaneously in the right flank with 10(6) MDA-MB-231 cells. When the tumor size reached ~0.6 cm(3), mice (n=9) were injected with ~37 MBq of (99m)Tc-MDP intravenously and then imaged one hour later in a NanoSPECT/CT or injected intravenously with 4 nmol/g of Osetosense 750EX and imaged 24 hours later in an FMT (n=4). The imaging probe concentration in the tumor was compared to that of muscle. Following SPECT imaging, the tumors were harvested, sectioned into 10 μm slices, and underwent autoradiography or von Kossa staining to correlate (99m)Tc-MDP binding with HAP distribution within the tumor. The SPECT images were normalized to the injected dose and regions-of-interest (ROIs) were drawn around bone, tumor, and muscle to obtain the radiotracer concentration in these regions in units of percent injected dose per unit volume. ROIs were drawn around bone and tumor in the FMT images as no FMT signal was observed in normal muscle.
  
  
  RESULTS
  Uptake of (99m)Tc-MDP was observed in the bone and tumor with little or no uptake in the muscle with concentrations of 11.34±1.46 (mean±SD), 2.22±0.95, and 0.05±0.04%ID/cc, respectively. Uptake of Osteosense 750EX was also observed in the bone and tumor with concentrations of 0.35±0.07 (mean±SD) and 0.04±0.01picomoles, respectively. No FMT signal was observed in the normal muscle. There was no significant difference in the bone-to-tumor ratio between the two modalities (5.1±2.3 for SPECT and 8.8±2.2 for FMT) indicating that there is little difference in tumor uptake between these two agents.
  
  
  CONCLUSIONS
  This study provides evidence of the accessibility of HAP within the breast tumor microenvironment as an in vivo imaging target for bone-seeking agents. SPECT imaging using (99m)Tc-MDP can be rapidly translated to the clinic. FMT imaging using Osteosense 750EX is not currently approved for clinical use and is limited to animal research.
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Dayo D
authors.initials: DD
authors.lastname: Felix
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Physics Astronomy, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Cancer Biology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Gore
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Physics Astronomy, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular physiology and Biophysics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Yankeelov
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Physics Astronomy, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Todd E
authors.initials: TE
authors.lastname: Peterson
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barnes
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Whisenant
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Weis
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Shoukouhi
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: John
authors.initials: J
authors.lastname: Virostko
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nickels
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular physiology and Biophysics, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: J Oliver
authors.initials: JO
authors.lastname: McIntyre
authors.affiliation: Department of Pathology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Sanders
authors.affiliation: Department of Hematology/Oncology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Abramson
authors.affiliation: Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA; Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA. Electronic address: mohammed.n.tantawy@vanderblt.edu.
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: Tantawy
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging; D001943:Breast Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging*; D002114:Calcinosis / Q000150:complications*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D061848:Optical Imaging; D013669:Technetium Tc 99m Medronate; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D013669:Technetium Tc 99m Medronate
keywords: (99m)Tc-MDP; Breast cancer; Hydroxyapetite; MDA-MB-231; Microcalcification; SPECT