PMID- 24516257 OWN - NLM STAT- MEDLINE DCOM- 20140429 LR - 20220408 IS - 1535-5667 (Electronic) IS - 0161-5505 (Linking) VI - 55 IP - 3 DP - 2014 Mar TI - Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer. PG - 386-91 LID - 10.2967/jnumed.113.120485 [doi] AB - 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: (18)F-FDG uptake ((18)F-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 (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), 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 (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes. FAU - Miles, Kenneth A AU - Miles KA AD - University College London/UCLH, London, United Kingdom; and. FAU - Ganeshan, Balaji AU - Ganeshan B FAU - Rodriguez-Justo, Manuel AU - Rodriguez-Justo M FAU - Goh, Vicky J AU - Goh VJ FAU - Ziauddin, Zia AU - Ziauddin Z FAU - Engledow, Alec AU - Engledow A FAU - Meagher, Marie AU - Meagher M FAU - Endozo, Raymondo AU - Endozo R FAU - Taylor, Stuart A AU - Taylor SA FAU - Halligan, Stephen AU - Halligan S FAU - Ell, Peter J AU - Ell PJ FAU - Groves, Ashley M AU - Groves AM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140210 PL - United States TA - J Nucl Med JT - Journal of nuclear medicine : official publication, Society of Nuclear Medicine JID - 0217410 RN - 0 (KRAS protein, human) RN - 0 (Proto-Oncogene Proteins) RN - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) RN - EC 3.6.5.2 (ras Proteins) SB - IM MH - Colorectal Neoplasms/*diagnosis/diagnostic imaging/*genetics MH - Decision Trees MH - Female MH - Humans MH - Male MH - Middle Aged MH - *Multimodal Imaging MH - *Mutation MH - *Positron-Emission Tomography MH - Proto-Oncogene Proteins/*genetics MH - Proto-Oncogene Proteins p21(ras) MH - *Tomography, X-Ray Computed MH - ras Proteins/*genetics OTO - NOTNLM OT - KRAS protein OT - colonic neoplasms OT - comparative study OT - diagnostic imaging OT - human EDAT- 2014/02/12 06:00 MHDA- 2014/04/30 06:00 CRDT- 2014/02/12 06:00 PHST- 2014/02/12 06:00 [entrez] PHST- 2014/02/12 06:00 [pubmed] PHST- 2014/04/30 06:00 [medline] AID - jnumed.113.120485 [pii] AID - 10.2967/jnumed.113.120485 [doi] PST - ppublish SO - J Nucl Med. 2014 Mar;55(3):386-91. doi: 10.2967/jnumed.113.120485. Epub 2014 Feb 10.