BACKGROUND: In previous work, we demonstrated the presence of hydroxyapetite (type II microcalcification), HAP, in triple negative MDA-MB-231 @entity0 cells. We used (18)F-NaF to detect these types of @entity5 in @entity19 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 @entity0 microenvironment. METHODS: Thirteen @entity19 were injected subcutaneously in the right flank with 10(6) MDA-MB-231 cells. When the @entity5 size reached ~0.6cm(3), @entity19 (n=9) were injected with ~37MBq of (99m)Tc-MDP intravenously and then imaged one hour later in a NanoSPECT/CT or injected intravenously with 4nmol/g of Osetosense 750EX and imaged 24hours later in an FMT (n=4). The imaging probe concentration in the @entity5 was compared to that of muscle. Following SPECT imaging, the @entity5 were harvested, sectioned into 10 m slices, and underwent autoradiography or von Kossa staining to correlate (99m)Tc-MDP binding with HAP distribution within the @entity5 . The SPECT images were normalized to the injected dose and regions-of-interest (ROIs) were drawn around bone, @entity5 , 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 @entity5 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 @entity5 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 @entity5 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- @entity5 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 @entity5 uptake between these two agents. CONCLUSION: This study provides evidence of the accessibility of @entity0 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.

Detection of XXXX using (99m)Tc-MDP SPECT or Osteosense 750EX FMT imaging.

@entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancers', 'tumors'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity0 :: ('MESH:D001943', 'Disease') :: ['HAP within the breast tumor', 'breast cancer', 'breast cancer diagnosis via targeting HAP within the tumor']
@entity0 :: (MESH:D001943,Disease) :: ['breast cancer microcalcification']
