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Cells in murine muscle have been reported to differentiate into hematopoietic stem and progenitor cells and thus repopulate the hematopoietic system of an irradiated animal. This activity was attributed to muscle stem cells. We used an in vitro and in vivo approach to identify the hematopoietic repopulating activity found in muscle tissue of mice by antibody staining and cell sorting. We confirmed existence of a hematopoietic repopulating cell in muscle tissue, but the data strongly suggest that repopulation is due not to muscle stem cells but to hematopoi-

Rationale Current radiological methods for diagnosing breast cancer detect specific morphological features of solid tumors and/or any associated calcium deposits. These deposits originate from an early molecular microcalcification process which consists of two types: type 1 is calcium oxylate (CO) and type II is carbonated calcium hydroxyapetite (HAP). Type I microcalcifications are mainly associated with benign tumors while type II have been shown to be produced, internally, by malignant cells. No current non-invasive in vivo techniques are available for detecting intratumoral microcalcifications. Such a technique would have a significant impact on breast cancer diagnosis and prognosis in preclinical and clinical settings. 18F-NaF PET has been solely used for bone imaging by targeting the bone HAP. In this work, we provide preliminary evidence that 18F-NaF PET imaging can be used to detect breast cancer by targeting the HAP lattice within the tumor microenvironment with high specificity and soft-tissue contrast-to-background ratio, while delineating tumors from inflammation. METHODS Mice were injected with approximately 106 MDA-MB-231 cells subcutaneously and imaged with 18F-NaF PET/CT in a 120 min dynamic sequence when the tumors reached a size of ~250 mm3. Regions-of-interest (ROIs) were drawn around the tumor, muscle, and bone. The concentration of the radiotracer within those ROIs were compared to one another. For comparison to inflammation, rats with inflammatory paws were subjected to 18F-NaF PET imaging. RESULTS Tumor uptake of 18F− was significantly higher (p<0.05) than muscle uptake where the tumor-to-muscle ratio was ~3.5. The presence of type II microcalcification in the MDA-MB-231 cell line was confirmed histologically using alizarin red S and von Kossa staining as well as Raman microspectroscopy. No uptake of 18F− was observed in the rat inflamed tissue. Lack of HAP in the inflamed tissue was verified histologically. CONCLUSIONS This study provides preliminary evidence suggesting that specific targeting of the HAP within the tumor microenvironment with 18F may be able to distinguishing between inflammation and cancer.