A study by Falou et al. also suggested that responders and nonresponders could be differentiated check details with DOS [26]. Finally, the

biomedical engineering group at Duke University (Durham, NC) showed that a combination of DRS and AFS can be applied to monitor drug concentrations and tumor physiology in vivo in a preclinical mouse model [27]. Studies thus far have mainly focused on the noninvasive application of optical sensing by hand-held optical transducers used to scan tissue surfaces. This approach has a clear advantage for breast tumors but may limit the applicability of optical sensing for deep-seeded tumors such as in the lung or kidney. Recently, we described an optical needle probe able to perform optical measurements in tumor tissue [21], [28] and [29]. Optical measurements conducted through very fine needles (smaller than 27 G) open the potential to assess treatment response of (solid) tumors at deep-tissue sites [30]. The aim of this study was to investigate whether dual-modality DRS-AFS, incorporated in a small needle probe,

was able to monitor the dynamics of tumor response after treatment with cisplatin using a preclinical mouse model for BRCA1-mutated BLZ945 in vitro breast cancer. In this study, Brca1−/−; p53−/− mammary tumors were generated in a mouse model for hereditary breast cancer previously described by Liu et al. [31]. These tumors have been demonstrated to be sensitive to cisplatin at a maximum tolerated dose (MTD) of 6 mg/kg i.v. [32]. Small fragments of tumor (1-2 mm in diameter) were orthotopically

transplanted into the fourth right mammary fat pad of 36 female (FVB/N HanHSD WT) animals (The Pyruvate dehydrogenase Netherlands Cancer Institute, Amsterdam, The Netherlands) (6-8 weeks of age) as described previously [32]. Starting 2 weeks after tumor grafting, the onset of tumor growth was checked at least three times per week. Tumor size was determined by caliper measurements (length and width in millimeters), and tumor volume (in cubic millimeters) was calculated using the following formula: 0.5 × length × width2. Once the tumor volume reached 400 to 800 mm3, the animals were separated into control and treatment groups. Animals in the treatment group (N = 18) received cisplatin (1 mg/ml in saline/mannitol) at a dose of 6 mg/kg (MTD) in a single i.v. injection into the tail vein. Animals in the control group (N = 18) received an equivalent amount of saline. DRS and AFS tumor measurements were performed in vivo after inserting the spectroscopy needle percutaneously (through the skin) into the tumors. Baseline measurements were performed on day 0, immediately after treatment/placebo administration, and then on days 1, 2, 4, and 7 afterwards. These time points were selected from a previous pilot study. To evaluate whether eventual changes in the optical profile were systemic or tumor specific, eight animals from each group were randomly chosen for additional in vivo measurements in liver and muscle tissues on days 2, 4, and 7.