MR imaging of tumor angiogenesis using sterically stabilized Gd-DTPA liposomes targeted to CD105.
OBJECTIVE
To depict tumor angiogenesis via the expression of CD105 in tumor-bearing rats using Gd-DTPA liposomes targeted to CD105 (CD105-Gd-SLs) on MR imaging.


METHODS
Three Gd-DTPA liposomal nanoparticles were prepared in our trial: liposomes entrapping Gd-DTPA (Gd-SLs), Gd-SLs conjugated to immunoglobulins (IgG-Gd-SLs) and CD105-Gd-SLs. Forty glioma-bearing rats were randomized into four groups: (a) Gd-DTPA; (b) Gd-SLs; (c) IgG-Gd-SLs; (d) CD105-Gd-SLs. Axial T1WI MRI images were collected at baseline and repeated at 5, 30, 60 and 120 min post-intravenous injection of Gd-DTPA or liposome. Enhancement features and contrast-to-noise ratio of each group were analyzed. After imaging, tumors were resected for immunohistochemistry and immunofluorescence staining to assess vascularity and angiogenesis.


RESULTS
The four groups showed different enhancement features. The enhancement area was restricted for group CD105-Gd-SLs, while diffused for the other three. The degree of enhancement over time varied: group Gd-DTPA showed an early contrast enhancement at instant after injection with a peak at 30 min and a decline to baseline values at 60 min. In group CD105-Gd-SLs, the signal intensity (SI) continuously increased over 120 min. In groups IgG-Gd-SLs and Gd-SLs the SI peaked at 60 min, followed by a minor decrease for IgG-Gd-SLs and a rapid decrease for Gd-SLs almost to baseline. Immunohistochemistry and immunofluorescence showed that the enhancement in the CD105-Gd-SLs group resulted mainly from new microvessels. While in the other three groups, mature microvessels and new microvasculature resulted in the enhancement of the tumor.


CONCLUSIONS
CD105-Gd-SLs can be used to detect early tumor angiogenesis on MR images. This might provide a means to non-invasively reveal a malignant phenotype of extracerebral F98 tumor and evaluate its progression.
Department of Radiology, XinQiao Hospital, Third Military Medical University, ChongQing 400037, PR China.
Dong
D
Zhang
Xiao-Yuan
XY
Feng
Tobias D
TD
Henning
Li
L
Wen
Wei-Yue
WY
Lu
Hong
H
Pan
Xing
X
Wu
Li-Guang
LG
Zou
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D000071063:Endoglin; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D005910:Glioma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D008081:Liposomes / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011956:Receptors, Cell Surface / Q000378:metabolism*
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D003287:Contrast Media; D004337:Drug Carriers; C064206:ENG protein, human; D000071063:Endoglin; D008081:Liposomes; D011956:Receptors, Cell Surface; D019786:Gadolinium DTPA