title: DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content.
abstract: OBJECTIVE
  To compare DCE-MRI experiments performed using a standard small-molecular (Gd-DTPA) and an albumin-binding (MS-325) contrast agent in two carcinoma models with different stromal content.
  
  
  METHODS
  DU-145 or BXPC-3 cancer cells were subcutaneously injected into nude mice. DCE-MRI was performed by a bolus injection of Gd-DTPA or MS-325 about 2 weeks after inoculation. For quantitative analysis a volume of interest was manually drawn over each tumor. To address the heterogeneous enhancement, each tumor volume was then divided into the 20% most-enhancing and the remaining 80% least-enhancing fractions. Mean tumor enhancement was calculated over these selected tumor volumes and compared between tumor groups and contrast agents. Maps of differential enhancement, peak enhancement and time-to-peak were used for visual evaluation. CD31 and VEGF immunohistochemistry were performed in excised tumors.
  
  
  RESULTS
  In the 80% least-enhancing volume, at late time points of the dynamic scan, the mean enhancement elicited by MS-325 was higher in BXPC-3 than in DU-145 tumors. In the 20% most-enhancing volume, using either contrast agents, significant difference between the two tumors types were observed only early, while at later time points of the dynamic scan the difference were obscured by the faster washout observed in the BXPC-3 tumors. Enhancement maps confirmed that BXPC-3 tumors were characterized by marked washout rate using either contrast agent, particularly in the higher enhancing peripheral rim. With MS-325 this washout pattern appeared to be specific to the BXPC-3 carcinomas, since it was not observed in the DU-145 tumors. Finally, in both tumor types, MS-325 produced significantly higher enhancement than Gd-DTPA in the late phase of the dynamic scan. Ex vivo analysis confirmed the marked presence of aberrant infiltrative stroma in BXPC-3 tumors, in which tumor vessels were embedded. In all tumors the central portion was less viable and less infiltrated by stromal tissue then the peripheral areas.
  
  
  CONCLUSIONS
  Contrast distribution proved to be related to stromal content, which presumably produced the higher enhancement and faster washout observed in the BXPC-3 tumors. In particular, 'early' contrast-enhanced MRI, appeared as the most sensitive technique to detect the tumor portions characterized by a high stromal content, i.e. the peripheral rim of the BXPC-3 tumors. Since the same tumor models were recently investigated using FDG-PET imaging, showing inverse relationship between FDG uptake and stromal content, contrast-enhanced MRI and FDG-PET could provide complementary and comprehensive sensitivity in the assessment of carcinomas.
authors.affiliation: Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Farace
authors.forename: Flavia
authors.initials: F
authors.lastname: Merigo
authors.forename: Silvia
authors.initials: S
authors.lastname: Fiorini
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolato
authors.forename: Stefano
authors.initials: S
authors.lastname: Tambalo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Daducci
authors.forename: Anna
authors.initials: A
authors.lastname: Degrassi
authors.forename: Andrea
authors.initials: A
authors.lastname: Sbarbati
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D005682:Gadolinium; D019786:Gadolinium DTPA; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000175:diagnosis*; D009942:Organometallic Compounds; D010190:Pancreatic Neoplasms / Q000175:diagnosis; D011471:Prostatic Neoplasms / Q000175:diagnosis
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D005682:Gadolinium; D019786:Gadolinium DTPA; C109932:gadofosveset trisodium