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Longitudinal measurement of subcutaneous and intratibial human prostate cancer xenograft growth and response to ionizing radiation by plasma Alu and LINE-1 ctDNA: A comparison to standard methods.
Mishra, Alok; Zennami, Kenji; Velarde, Esteban; Thorek, Daniel L J; Yegnasubramanian, Srinivasan; DeWeese, Theodore L; Lupold, Shawn E.
Afiliação
  • Mishra A; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Zennami K; Department of Urology, The James Buchanan Brady Urologic Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Velarde E; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Thorek DLJ; Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Yegnasubramanian S; Department of Radiology and Biomedical Engineering, Washington University School of Medicine, St. Louis, Missouri, USA.
  • DeWeese TL; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Lupold SE; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Prostate ; 81(11): 745-753, 2021 08.
Article em En | MEDLINE | ID: mdl-34032307
ABSTRACT

BACKGROUND:

Current preclinical models of metastatic prostate cancer (PCa) require sophisticated technologies and/or genetically engineered cells for the noninvasive monitoring of tumors in remote sites, such as bone. Recent developments in circulating tumor DNA (ctDNA) analysis provide an alternative method for noninvasive tumor monitoring at a low cost. Here, we sought to evaluate human Alu and LINE-1 ctDNA for the longitudinal measurement of subcutaneous and intratibial human PCa xenograft growth and response to ionizing radiation (IR) through comparison with standard slide caliper and bioluminescence measurements. MATERIAL AND

METHODS:

Intratibial and subcutaneous xenografts were established in male athymic nude mice using LNCaP cells that stably express firefly luciferase. A subset of tumors was treated with a single dose of IR (CT-guided focal IR, 6 Gy). Tumor measurements were simultaneously taken by slide caliper (subcutaneous only), in vivo bioluminescence imaging, and quantitative real-time PCR (qPCR) of human-specific Alu and LINE-1 ctDNA for several weeks.

RESULTS:

Levels of ctDNA and bioluminescence increased concordantly with subcutaneous and intratibial tumor growth. A statistically significant correlation (Spearman) was observed between ctDNA and subcutaneous tumor volume (LINE-1, r = .94 and Alu, r = .95, p < .0001), ctDNA and bioluminescence (LINE-1, r = .66 and Alu, r = .60, p < .002), and bioluminescence and tumor volume (r = .66, p = .0003). Bioluminescence and ctDNA were also significantly correlated in intratibial tumors (LINE-1, r = .82 and Alu, r = .81, p < .0001). Following external beam IR, the tumor responses varied briefly by method of measurement, but followed a similar trend. Statistically significant correlations were maintained between ctDNA and slide caliper measurement in irradiated subcutaneous tumors (LINE-1, r = .64 and Alu, r = .44, p < .02), and ctDNA and bioluminescence in intratibial tumors (LINE-1, r = .55, p = .018).

CONCLUSIONS:

Real-time qPCR of circulating human Alu and LINE-1 DNA provides an accurate measurement of subcutaneous and intratibial xenograft burden that is comparable with conventional bioluminescence imaging and slide caliper measurement. Transient differences in measurements were observed following tumor-targeted IR, but overall all measurements mirrored tumor growth and response.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Elementos Nucleotídeos Longos e Dispersos / Elementos Alu / Ensaios Antitumorais Modelo de Xenoenxerto / DNA Tumoral Circulante Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias da Próstata / Elementos Nucleotídeos Longos e Dispersos / Elementos Alu / Ensaios Antitumorais Modelo de Xenoenxerto / DNA Tumoral Circulante Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article