title: Characterization and longitudinal monitoring of melanoma growth in ret-transgenic mice using a single-sequence MRI protocol.
abstract: Spontaneous melanoma models in transgenic mice are increasingly used in preclinical research as they most closely match the progression of melanoma in humans. While optical inspection only allows analysis of tumors located on the skin, the accurate measurement and growth of subcutaneous tumors have not been adequately assessed. To improve the measurement accuracy of melanoma tumors, we used a fast single-sequence MRI protocol at 9.4 Tesla for longitudinal characterization of a ret-transgenic mouse model. Repeated MRI (average acquisition time 30 min per animal) of the trunk (excluding head and distal limbs) in six siblings revealed an increase in the mean total tumor volume (TTV) from 102.0 ± 80.5 mm(3) at 35 days of age to 434.8 ± 154.9 mm(3) by 77 days. The main tumor load was located within the pelvis (>40%), followed by the proximal hind limbs and groins (>30%). The smallest detectable tumor measured 0.07 mm(3). Inter-rater reliability between a radiologist and a veterinarian analysing MRI data was 0.993 for TTV and 0.840 for number of tumors (both p < 0.001). We thus conclude that because of the high variance of TTV of same-aged mice, MRI should be used (i) to establish treatment groups matched for TTV and (ii) for longitudinal examination of the TTV in mice over the course of treatments.
authors.affiliation: Department of Neuroradiology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Hans U
authors.initials: HU
authors.lastname: Kerl
authors.forename: Hanne
authors.initials: H
authors.lastname: Boll
authors.forename: Marcel
authors.initials: M
authors.lastname: Ramacher
authors.forename: Melanie
authors.initials: M
authors.lastname: Heilmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Groden
authors.forename: Martin
authors.initials: M
authors.lastname: Kramer
authors.forename: Viktor
authors.initials: V
authors.lastname: Umansky
authors.forename: Marc A
authors.initials: MA
authors.lastname: Brockmann
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015588:Observer Variation; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D047368:Tumor Burden
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse