Accurate isolation and detection of circulating tumor cells using enrichment-free multiparametric high resolution imaging

Dannel Yeo; Dannel Yeo; Dannel Yeo; Dannel Yeo; Steven Kao; Steven Kao; Ruta Gupta; Ruta Gupta; Ruta Gupta; Sara Wahlroos; Althea Bastian; Althea Bastian; Althea Bastian; Althea Bastian; Heidi Strauss; Heidi Strauss; Heidi Strauss; Heidi Strauss; Vera Klemm; Vera Klemm; Vera Klemm; Vera Klemm; Prajwol Shrestha; Prajwol Shrestha; Prajwol Shrestha; Prajwol Shrestha; Arturo B. Ramirez; Lillian Costandy; Ryan Huston; Brady S. Gardner; Peter Grimison; Peter Grimison; Jonathan R. Clark; Jonathan R. Clark; Jonathan R. Clark; John E. J. Rasko; John E. J. Rasko; John E. J. Rasko; John E. J. Rasko

doi:10.3389/fonc.2023.1141228

Frontiers in Oncology (Mar 2023)

Accurate isolation and detection of circulating tumor cells using enrichment-free multiparametric high resolution imaging

Dannel Yeo,
Dannel Yeo,
Dannel Yeo,
Dannel Yeo,
Steven Kao,
Steven Kao,
Ruta Gupta,
Ruta Gupta,
Ruta Gupta,
Sara Wahlroos,
Althea Bastian,
Althea Bastian,
Althea Bastian,
Althea Bastian,
Heidi Strauss,
Heidi Strauss,
Heidi Strauss,
Heidi Strauss,
Vera Klemm,
Vera Klemm,
Vera Klemm,
Vera Klemm,
Prajwol Shrestha,
Prajwol Shrestha,
Prajwol Shrestha,
Prajwol Shrestha,
Arturo B. Ramirez,
Lillian Costandy,
Ryan Huston,
Brady S. Gardner,
Peter Grimison,
Peter Grimison,
Jonathan R. Clark,
Jonathan R. Clark,
Jonathan R. Clark,
John E. J. Rasko,
John E. J. Rasko,
John E. J. Rasko,
John E. J. Rasko

Affiliations

Dannel Yeo: Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW, Australia
Dannel Yeo: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Dannel Yeo: Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW, Australia
Dannel Yeo: Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW, Australia
Steven Kao: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Steven Kao: Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia
Ruta Gupta: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Ruta Gupta: Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse, Camperdown, NSW, Australia
Ruta Gupta: NSW Health Pathology, Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW, Australia
Sara Wahlroos: Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia
Althea Bastian: Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW, Australia
Althea Bastian: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Althea Bastian: Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW, Australia
Althea Bastian: Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW, Australia
Heidi Strauss: Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW, Australia
Heidi Strauss: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Heidi Strauss: Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW, Australia
Heidi Strauss: Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW, Australia
Vera Klemm: Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW, Australia
Vera Klemm: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Vera Klemm: Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW, Australia
Vera Klemm: Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW, Australia
Prajwol Shrestha: Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW, Australia
Prajwol Shrestha: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Prajwol Shrestha: Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW, Australia
Prajwol Shrestha: Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia
Arturo B. Ramirez: RareCyte Inc., Seattle, WA, United States
Lillian Costandy: RareCyte Inc., Seattle, WA, United States
Ryan Huston: RareCyte Inc., Seattle, WA, United States
Brady S. Gardner: RareCyte Inc., Seattle, WA, United States
Peter Grimison: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Peter Grimison: Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW, Australia
Jonathan R. Clark: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
Jonathan R. Clark: Department of Head and Neck Surgery, Sydney Head and Neck Cancer Institute, Chris O’Brien Lifehouse, Camperdown, NSW, Australia
Jonathan R. Clark: Royal Prince Alfred Institute of Academic Surgery, Sydney Local Health District, Camperdown, NSW, Australia
John E. J. Rasko: Li Ka Shing Cell & Gene Therapy Program, The University of Sydney, Camperdown, NSW, Australia
John E. J. Rasko: Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia
John E. J. Rasko: Cell and Molecular Therapies, Royal Prince Alfred Hospital, Sydney Local Health District, Camperdown, NSW, Australia
John E. J. Rasko: Gene and Stem Cell Therapy Program Centenary Institute, The University of Sydney, Camperdown, NSW, Australia

DOI: https://doi.org/10.3389/fonc.2023.1141228
Journal volume & issue: Vol. 13

Abstract

Read online

IntroductionThe reliable and accurate detection of rare circulating tumor cells (CTCs) from cancer patient blood samples promises advantages in both research and clinical applications. Numerous CTC detection methods have been explored that rely on either the physical properties of CTCs such as density, size, charge, and/or their antigen expression profiles. Multiple factors can influence CTC recovery including blood processing method and time to processing. This study aimed to examine the accuracy and sensitivity of an enrichment-free method of isolating leukocytes (AccuCyte® system) followed by immunofluorescence staining and high-resolution imaging (CyteFinder® instrument) to detect CTCs.MethodHealthy human blood samples, spiked with cancer cells from cancer cell lines, as well as blood samples obtained from 4 subjects diagnosed with cancer (2 pancreatic, 1 thyroid, and 1 small cell lung) were processed using the AccuCyte-CyteFinder system to assess recovery rate, accuracy, and reliability over a range of processing times.ResultsThe AccuCyte-CyteFinder system was highly accurate (95.0%) at identifying cancer cells in spiked-in samples (in 7.5 mL of blood), even at low spiked-in numbers of 5 cells with high sensitivity (90%). The AccuCyte-CyteFinder recovery rate (90.9%) was significantly higher compared to recovery rates obtained by density gradient centrifugation (20.0%) and red blood cell lysis (52.0%). Reliable and comparable recovery was observed in spiked-in samples and in clinical blood samples processed up to 72 hours post-collection. Reviewer analysis of images from spiked-in and clinical samples resulted in high concordance (R-squared value of 0.998 and 0.984 respectively).DiscussionThe AccuCyte-CyteFinder system is as an accurate, sensitive, and clinically practical method to detect and enumerate cancer cells. This system addresses some of the practical logistical challenges in incorporating CTCs as part of routine clinical care. This could facilitate the clinical use of CTCs in guiding precision, personalized medicine.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

About the journal

Abstract

Keywords