UNLABELLED Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker... Show moreUNLABELLED Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker. METHODS A hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry-based target validation in fresh tumor tissue to in vivo single photon emission computed tomography (SPECT) imaging and in vivo and ex vivo fluorescence imaging. RESULTS Flow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4(basal), CXCR4(+) and CXCR4(++) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry. CONCLUSION The hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches. Show less
Buckle, T.; Kuil, J.; Berg, N.S. van den; Bunschoten, A.; Lamb, H.J.; Yuan, H.H.; ... ; Leeuwen, F.W.B. van 2013
α(v)β(3) integrin is involved in (tumor-induced) angiogenesis and is a promising candidate for the specific visualization of both primary tumors and of their distant metastases. Combination of... Show moreα(v)β(3) integrin is involved in (tumor-induced) angiogenesis and is a promising candidate for the specific visualization of both primary tumors and of their distant metastases. Combination of radioactive and fluorescent imaging labels in a single multimodal, or rather hybrid, RGD-based imaging agent enables integration of pre-, intra-, and postoperative angiogenesis imaging. A hybrid imaging agent targeting the α(v)β(3) integrin--(111)In-MSAP-RGD (MSAP = multifunctional single-attachment-point reagent), which contains a targeting moiety, a pentetic acid (DTPA) chelate, and a cyanine dye--was evaluated for its potential value in combined lesion detection and interventional molecular imaging in a 4T1 mouse breast cancer model. SPECT/CT and fluorescence imaging were used to visualize the tumor in vivo. Tracer distribution was evaluated ex vivo down to the microscopic level. The properties of (111)In-MSAP-RGD were compared with those of (111)In-DTPA-RGD. Biodistribution studies revealed a prolonged retention and increased tumor accumulation of (111)In-MSAP-RGD relative to (111)In-DTPA-RGD. With (111)In-MSAP-RGD, identical features could be visualized preoperatively (SPECT/CT) and intraoperatively (fluorescence imaging). As well as the primary tumor, (111)In-MSAP-RGD also enabled detection and accurate excision of distant metastases in the head and neck region of the mice. Therefore, the hybrid RGD derivative (111)In-MSAP-RGD shows potential in preoperative planning and fluorescence-based surgical intervention. Show less
