Abstract
In animal studies tumor size is used to assess responses to anticancer therapy. Current standard for volumetric measurement of xenografted tumors is by external caliper, a method often affected by error. The aim of the present study was to evaluate if microCT gives more accurate and reproducible measures of tumor size in mice compared with caliper measurements. Furthermore, we evaluated the accuracy of tumor volume determined from 18F-fluorodeoxyglucose (18F-FDG) PET. Subcutaneously implanted human breast adenocarcinoma cells in NMRI nude mice served as tumor model. Tumor volume (n = 20) was determined in vivo by external caliper, microCT and 18F-FDG-PET and subsequently reference volume was determined ex vivo. Intra-observer reproducibility of the microCT and caliper methods were determined by acquiring 10 repeated volume measurements. Volumes of a group of tumors (n = 10) were determined independently by two observers to assess inter-observer variation. Tumor volume measured by microCT, PET and caliper all correlated with reference volume. No significant bias of microCT measurements compared with the reference was found, whereas both PET and caliper had systematic bias compared to reference volume. Coefficients of variation for intra-observer variation were 7% and 14% for microCT and caliper measurements, respectively. Regression coefficients between observers were 0.97 for microCT and 0.91 for caliper measurements. MicroCT was more accurate than both caliper and 18F-FDG-PET for in vivo volumetric measurements of subcutaneous tumors in mice.18F-FDG-PET was considered unsuitable for determination of tumor size. External caliper were inaccurate and encumbered with a significant and size dependent bias. MicroCT was also the most reproducible of the methods.
MeSH Terms
Adenocarcinoma/diagnosis
Animals
Breast Neoplasms/diagnosis
Fluorodeoxyglucose F18
Humans
Mice
Mice, Nude
Physical Examination/methods
Positron-Emission Tomography/methods,veterinary
Radiopharmaceuticals
Reproducibility of Results
Sensitivity and Specificity
Tomography, X-Ray Computed/methods,veterinary
Chemicals
Radiopharmaceuticals
Fluorodeoxyglucose F18
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jensen Mette Munk
Cluster for Molecular Imaging, University of Copenhagen, Copenhagen, Denmark. mettemj@mfi.ku.dk
Jørgensen Jesper Tranekjaer
Binderup Tina
Kjaer Andreas
References (12)
12 references, click to expand
-
Statistical methods for assessing agreement between two methods of clinical measurement.
Lancet. 1986 Feb 8;1(8476):307-10
PMID: 2868172
-
Tumor measurement in the nude mouse.
J Surg Oncol. 1986 Apr;31(4):229-34
PMID: 3724177
-
Determination of subcutaneous tumor size in athymic (nude) mice.
Cancer Chemother Pharmacol. 1989;24(3):148-54
PMID: 2544306
-
Magnetic resonance imaging of response to chemotherapy in orthotopic xenografts of human bladder cancer.
Clin Cancer Res. 1997 Sep;3(9):1635-41
PMID: 9815854
-
Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy-3'-18F-fluorothymidine PET.
J Nucl Med. 2005 Jan;46(1):114-20
PMID: 15632041
-
Monitoring response to radiotherapy in human squamous cell cancer bearing nude mice: comparison of 2'-deoxy-2'-[18F]fluoro-D-glucose (FDG) and 3'-[18F]fluoro-3'-deoxythymidine (FLT).
Mol Imaging Biol. 2007 Nov-Dec;9(6):340-7
PMID: 17643202
-
Three-dimensional ultrasound biomicroscopy for xenograft growth analysis.
Ultrasound Med Biol. 2005 Jun;31(6):865-70
PMID: 15936502
-
Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033.
Eur J Nucl Med Mol Imaging. 2006 Apr;33(4):441-52
PMID: 16450138
-
Monitoring chemotherapy and radiotherapy of solid tumors.
Eur J Nucl Med Mol Imaging. 2006 Jul;33 Suppl 1:27-37
PMID: 16688451
-
In vivo biological activity of the histone deacetylase inhibitor LAQ824 is detectable with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.
Cancer Res. 2006 Aug 1;66(15):7621-9
PMID: 16885362
-
Monitoring tumor glucose utilization by positron emission tomography for the prediction of treatment response to epidermal growth factor receptor kinase inhibitors.
Clin Cancer Res. 2006 Oct 1;12(19):5659-67
PMID: 17020967
-
Tumor response assessment is more robust with sequential CT scanning than external caliper measurements.
Acad Radiol. 2005 Jun;12(6):776-81
PMID: 15935976