Gadopentetate dimeglumine versus ultrasmall superparamagnetic iron oxide for dynamic contrast-enhanced MR imaging of tumor angiogenesis in human colon carcinoma in mice.
OBJECTIVE
To compare the kinetic physiologic properties of a clinical contrast agent, gadopentetate dimeglumine, with those of ultrasmall superparamagnetic iron oxide (USPIO) particles for dynamic contrast material-enhanced magnetic resonance (MR) imaging of tumor angiogenesis in human colon carcinoma in mice with a clinical MR imaging unit.


METHODS
Thirty-two mice with human colon carcinoma were injected with either gadopentetate dimeglumine (n = 16) or USPIO (n = 16) for dynamic contrast-enhanced MR imaging and pre- and postcontrast T2 and T2* measurements. Dynamic contrast-enhanced MR imaging measurements were analyzed by using a two-compartment model to calculate the endothelial transfer coefficient surface area product (KPS) for the tumor microvasculature, the reflux coefficient (k), and the fractional plasma volume (fPV). KPS, k, and fPV maps were compared with histologic microvessel density (MVD) and used to observe differences between core and rim regions of tumor.


RESULTS
Results in 30 mice (15 in the gadopentetate dimeglumine group and 15 in the USPIO group) could be used. KPS values measured with both agents correlated well with MVD in hot spots (gadopentetate dimeglumine: r = 0.6, P =.02; USPIO: r = 0.6, P =.01). No significant difference (P =.4) in correlation was found between the two agents. Both USPIO and gadopentetate dimeglumine demonstrated higher MVD and KPS values in tumor rim than in tumor core (P <.01). Tumor k values correlated poorly with whole-tumor MVD for both gadopentetate dimeglumine (r = 0.3, P =.4) and USPIO (r = 0.2, P =.6), while fPV values correlated well with whole-tumor MVD for USPIO (r = 0.6, P =.02) but not gadopentetate dimeglumine (r = -0.01, P =.98). T2 and T2* measurements showed small differences between areas of high and low angiogenic activity with both agents.


CONCLUSIONS
The kinetic physiologic properties of gadopentetate dimeglumine are as good as those of USPIO for dynamic contrast-enhanced MR imaging for calculating KPS as a measurement of angiogenesis in human colon carcinoma. Further studies with patients may reveal whether gadopentetate dimeglumine might be used for this purpose in clinical practice.
Department of Radiology, Maastricht University Hospital, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, the Netherlands. qdlu@rdia.azm.nl
Quido G
QG
de Lussanet
Walter H
WH
Backes
Arjan W
AW
Griffioen
Jos M A
JM
van Engelshoven
Regina G H
RG
Beets-Tan
D000818:Animals; D002277:Carcinoma / Q000098:blood supply* / Q000175:diagnosis / Q000473:pathology; D003110:Colonic Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000473:pathology; D003287:Contrast Media; D003911:Dextrans; D052203:Ferrosoferric Oxide; D019786:Gadolinium DTPA; D066298:In Vitro Techniques; D007501:Iron; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000175:diagnosis*; D010087:Oxides
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D010087:Oxides; C097921:ferumoxtran-10; D007501:Iron; D019786:Gadolinium DTPA; D052203:Ferrosoferric Oxide