title: Detection of live circulating tumor cells by a class of near-infrared heptamethine carbocyanine dyes in patients with localized and metastatic prostate cancer.
abstract: Tumor cells are inherently heterogeneous and often exhibit diminished adhesion, resulting in the shedding of tumor cells into the circulation to form circulating tumor cells (CTCs). A fraction of these are live CTCs with potential of metastatic colonization whereas others are at various stages of apoptosis making them likely to be less relevant to understanding the disease. Isolation and characterization of live CTCs may augment information yielded by standard enumeration to help physicians to more accurately establish diagnosis, choose therapy, monitor response, and provide prognosis. We previously reported on a group of near-infrared (NIR) heptamethine carbocyanine dyes that are specifically and actively transported into live cancer cells. In this study, this viable tumor cell-specific behavior was utilized to detect live CTCs in prostate cancer patients. Peripheral blood mononuclear cells (PBMCs) from 40 patients with localized prostate cancer together with 5 patients with metastatic disease were stained with IR-783, the prototype heptamethine cyanine dye. Stained cells were subjected to flow cytometric analysis to identify live (NIR(+)) CTCs from the pool of total CTCs, which were identified by EpCAM staining. In patients with localized tumor, live CTC counts corresponded with total CTC numbers. Higher live CTC counts were seen in patients with larger tumors and those with more aggressive pathologic features including positive margins and/or lymph node invasion. Even higher CTC numbers (live and total) were detected in patients with metastatic disease. Live CTC counts declined when patients were receiving effective treatments, and conversely the counts tended to rise at the time of disease progression. Our study demonstrates the feasibility of applying of this staining technique to identify live CTCs, creating an opportunity for further molecular interrogation of a more biologically relevant CTC population.
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Department of Urology Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shao
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America.
authors.forename: Chun-Peng
authors.initials: CP
authors.lastname: Liao
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America.
authors.forename: Peizhen
authors.initials: P
authors.lastname: Hu
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America.
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Chu
authors.affiliation: Department of Epidemiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Divsion of Urology- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Matthew H T
authors.initials: MH
authors.lastname: Bui
authors.affiliation: Divsion of Urology- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Ng
authors.affiliation: Divsion of Urology- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: David Y
authors.initials: DY
authors.lastname: Josephson
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Translational Pathology and Biobank, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Knudsen
authors.affiliation: Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Mourad
authors.initials: M
authors.lastname: Tighiouart
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Divsion of Urology- Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Hyung L
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America.
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Division of Hematology Oncology-Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Division of Hematology Oncology-Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Ruoxiang
authors.initials: R
authors.lastname: Wang
authors.affiliation: Uro-Oncolgy Research Laboratories, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Urologic Oncology Program, Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angles, California, United States of America ; Division of Hematology Oncology-Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Posadas
mesh_terms: D002138:Calibration; D002232:Carbocyanines; D002452:Cell Count; D045744:Cell Line, Tumor; D002469:Cell Separation; D004396:Coloring Agents; D018450:Disease Progression; D006801:Humans; D007259:Infrared Rays; D008297:Male; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000601:surgery
chemical_list: D002232:Carbocyanines; D004396:Coloring Agents