Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer

Journal of Nuclear Medicine

Manuel Rodriguez-Justo¹  Stephen Halligan¹  Alec Engledow¹  Ashley M. Groves¹  Marie Meagher¹  Vicky J. Goh¹  Raymondo Endozo¹  Zia Ziauddin¹  Kenneth A. Miles¹  Balaji Ganeshan¹  Peter J. Ell¹  Stuart A. Taylor¹ 

关键词: KRAS protein;    human;    diagnostic imaging;    colonic neoplasms;    comparative study;   

DOI  :  10.2967/jnumed.113.120485

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. Methods: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: 18F-FDG uptake (18F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. Results: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%–93.9%), 0% (0%–10.4%), and 90.1% (79.2%–96.0%), respectively. KRAS mutants with high 18F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low 18F-FDG SUVmax, high MPP, and high blood flow expressed mcm2 (P = 0.036). Conclusion: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor 18F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

【 授权许可】

Unknown