A temporary indwelling intravascular aphaeretic system for in vivo enrichment of circulating tumor cells

• Published in: Nature communications 2019-04, Vol.10 (1), p.1478-1478, Article 1478
• Main Authors: Kim, Tae Hyun, Wang, Yang, Oliver, C. Ryan, Thamm, Douglas H., Cooling, Laura, Paoletti, Costanza, Smith, Kaylee J., Nagrath, Sunitha, Hayes, Daniel F.
• Format: Article
• Language: English
• Subjects: 13/62; 14/1; 14/34; 14/63; 147/135; 631/61/350; 631/67; 692/4028/67; 692/53; 82/47; 82/80; Animals; Biomarkers; Blood; Cancer; Carcinoma; Catheters; Cell Line, Tumor; Cell Separation - instrumentation; Cell Separation - methods; Computer engineering; Decision analysis; Design; Dogs; Enrichment; Graphene; Heterogeneity; Humanities and Social Sciences; Humans; Interrogation; MCF-7 Cells; Metastasis; multidisciplinary; Neoplastic Cells, Circulating; Phlebotomy; Printing, Three-Dimensional; Prognosis; Prostate; Science; Science (multidisciplinary); Tumor cells; Tumors; Veins & arteries
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09439-9

Circulating tumor cells (CTCs) have become an established biomarker for prognosis in patients with various carcinomas. However, current ex vivo CTC isolation technologies rely on small blood volumes from a single venipuncture limiting the number of captured CTCs. This produces statistical variability and inaccurate reflection of tumor cell heterogeneity. Here, we describe an in vivo indwelling intravascular aphaeretic CTC isolation system to continuously collect CTCs directly from a peripheral vein. The system returns the remaining blood products after CTC enrichment, permitting interrogation of larger blood volumes than classic phlebotomy specimens over a prolonged period of time. The system is validated in canine models showing capability to screen 1–2% of the entire blood over 2 h. Our result shows substantial increase in CTC capture, compared with serial blood draws. This technology could potentially be used to analyze large number of CTCs to facilitate translation of analytical information into future clinical decisions. Ex vivo methods of circulating tumor cell (CTC) isolation use small blood volumes, limiting sensitivity and introducing analytical inaccuracies. The authors describe a proof-of-concept study of an in vivo aphaeresis system that continuously collects CTCs from a peripheral vein over several hours.