title: Dynamic T1-weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging.
abstract: Studies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom-developed animal coil in a conventional whole-body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd-DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (k(ep)) were calculated according to a 2-compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High-resolution imaging of small heterotransplants from 100 to 1,000 mm(3) was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and k(ep) values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of k(ep) value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole-body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies.
authors.affiliation: Division of Oncological Diagnostics and Therapy, German Cancer Research Center, Heidelberg, Germany. F.Kiessling@dkfz.de
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
authors.forename: Melanie
authors.initials: M
authors.lastname: Heilmann
authors.forename: Silvia
authors.initials: S
authors.lastname: Vosseler
authors.forename: Matthias
authors.initials: M
authors.lastname: Lichy
authors.forename: Martin
authors.initials: M
authors.lastname: Krix
authors.forename: Christian
authors.initials: C
authors.lastname: Fink
authors.forename: Isabel
authors.initials: I
authors.lastname: Kiessling
authors.forename: Heinrich
authors.initials: H
authors.lastname: Steinbauer
authors.forename: Lothar
authors.initials: L
authors.lastname: Schad
authors.forename: Norbert E
authors.initials: NE
authors.lastname: Fusenig
authors.forename: Stefan
authors.initials: S
authors.lastname: Delorme
mesh_terms: D000769:Anesthesia, Inhalation; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology; D002461:Cell Line, Transformed / Q000637:transplantation; D003287:Contrast Media; D003626:Data Display; D019786:Gadolinium DTPA; D011905:Genes, ras; D006221:Halothane; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000295:instrumentation; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*; D014183:Transplantation, Heterologous
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA; D006221:Halothane