The detection and characterization of circulating tumor cells (CTC) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity, and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using surfaceenhanced Raman spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor peptide as a targeting ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1 to 720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers. Cancer Res; 71(5); 1526-32. Ó2011 AACR.

Quantum dot bioconjugates can be used for multiplexed and quantitative detection of tumor biomarkers in cells and tissues. This new technology should have significant impact on molecular pathology if validated with traditional techniques (such as western blotting, FISH, and IHC), and with large‐scale clinical studies. In addition, it could also become the first clinical application of quantum dots.

Angiogenesis and lymphangiogenesis are essential for breast cancer progression and are regulated by vascular endothelial growth factors (VEGF). To determine clinical and molecular correlates of these processes, we measured blood and lymphatic vascular microvessel density in 29 invasive carcinomas (22 ductal, six lobular, one papillary), using the vascular marker CD31 and the novel lymphatic marker D2-40. Microvessel density was assessed microscopically and by image cytometry, and was compared with tumor histology, grade, stage, lymph node metastasis, hormone receptors, HER2/neu status, and expression of VEGF, VEGF-C and VEGF-D by immunohistochemistry or quantitative RT-PCR. Strong correlation was observed between visual and image cytometric microvessel density using D2-40 but not CD31 (P ¼ 0.016 and 0.1521, respectively). Image cytometric CD31 microvessel density correlated with tumor size, grade, stage and lymph node metastasis (P ¼ 0.0001, 0.0107, 0.0035 and 0.0395, respectively). D2-40 microvessel density correlated with tumor stage (P ¼ 0.0123 by image cytometry) and lymph node metastasis (P ¼ 0.0558 by microscopy). Immunohistochemical VEGF signal in peritumoral blood vessels correlated with image cytometric CD31 and D2-40 microvessel density (P ¼ 0.022 and 0.0012, respectively), consistent with the role of VEGF in blood and lymphatic vascular growth. Intratumoral VEGF-C and VEGF-D expression by quantitative RT-PCR correlated with D2-40 (P ¼ 0.0291 by image cytometry) but not with CD31 microvessel density, which could suggest a selective role of VEGF-C and VEGF-D in lymphangiogenesis. CD31 and D2-40 microvessel density correlated significantly with several prognostic factors, including lymph node metastasis. Thus, measurements of angiogenesis and lymphangiogenesis may have utility for breast cancer pathology, particularly for estimation of metastatic risk. Angiogenesis (blood vessel growth) and lymphangiogenesis (lymph vessel growth) are critical processes for tumor growth, invasion and metastasis.

Purpose:To compare the diagnostic performance of the synthetic amino acid analog radiotracer anti -1-amino-3-fl uorine 18-fl uorocyclobutane-1-carboxylic acid ( anti -3-18 F-FACBC) with that of indium 111 ( 111 In)-capromab pendetide in the detection of recurrent prostate carcinoma. Materials andMethods:This prospective study was approved by the institutional review board and complied with HIPAA guidelines. Written informed consent was obtained. In-capromab pendetide single photon emission computed tomography (SPECT)/CT were performed within 6 weeks of each other. Studies were evaluated by two experienced interpreters for abnormal uptake suspicious for recurrent disease in the prostate bed and extraprostatic locations. The reference standard was a combination of tissue correlation , imaging, laboratory, and clinical data. Diagnostic performance measures were calculated and tests of the statistical signifi cance of differences determined by using the McNemar x 2 test as well as approximate tests based on the difference between two proportions. Results:For disease detection in the prostate bed, anti -3-18 F-FACBC had a sensitivity of 89 % (32 of 36 patients; 95% confi dence interval [CI]: 74%, 97%), specifi city of 67% (eight of 12 patients; 95% CI: 35%, 90%), and accuracy of 83% (40 of 48 patients; 95% CI: 70%, 93%).111 In-capromab pendetide had a sensitivity of 69% (25 of 36 patients; 95% CI: 52%, 84%), specifi city of 58% (seven of 12 patients; 95% CI: 28%, 85%), and accuracy of 67% (32 of 48 patients; 95% CI: 52%, 80%). In the detection of extraprostatic recurrence, anti -3-18 F-FACBC had a sensitivity of 100% (10 of 10 patients; 95% CI: 69%, 100%), specifi city of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 100% (17 of 17 patients; 95% CI: 80%, 100%).111 In-capromab pendetide had a sensitivity of 10% (one of 10 patients; 95% CI: 0%, 45%), specifi city of 100% (seven of seven patients; 95% CI: 59%, 100%), and accuracy of 47% (eight of 17 patients; 95% CI: 23%, 72%). Conclusion:anti -3-18 F-FACBC PET/CT was more sensitive than 111 Incapromab pendetide SPECT/CT in the detection of recurrent prostate carcinoma and is highly accurate in the differentiation of prostatic from extraprostatic disease.