Drug-induced vessel remodeling in bone metastases as assessed by dynamic contrast enhanced magnetic resonance imaging and vessel size imaging: a longitudinal in vivo study.
OBJECTIVE
The aim of this study was to assess the antiangiogenic treatment effects of zoledronic acid (ZA) and sunitinib malate (SM) noninvasively in experimental breast cancer bone metastases by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging.


METHODS
Nude rats bearing bone metastases after inoculation of MDA-MB-231 breast cancer cells were treated with ZA (40 microg/kg weekly; n = 8 rats), SM (20 mg/kg daily; n = 8 rats), or their combination (ZA and SM; n = 8 rats) and compared with sham-treated controls (n = 10 rats). Vascular changes in bone metastases were longitudinally imaged in vivo using DCE-MRI [amplitude (A) and exchange rate coefficient (k(ep))] and vessel size imaging [blood volume (BV) and vessel size index (VI)]. In addition, antiresorptive and antitumor changes were assessed in these lesions by flat-panel volumetric computed tomography as well as morphologic MRI and diffusion-weighted imaging.


RESULTS
In bone metastases, significant changes in A, k(ep), BV, and VI in accordance with decreased blood volume and vessel permeability as well as with increased mean vessel diameters were observed after application of ZA and SM as compared with controls. In this longitudinal study, antiangiogenic changes preceded the inhibition of osteolysis and antitumor effects after treatment.


CONCLUSIONS
These results indicate vessel remodeling in breast cancer bone metastases on ZA and SM treatment and implicate substantial effects on imaging and treatment of malignant bone lesions.
Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany. t.baeuerle@dkfz.de
Tobias
T
Bäuerle
Maximilian
M
Merz
Dorde
D
Komljenovic
Stefan
S
Zwick
Wolfhard
W
Semmler
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000473:pathology; D001859:Bone Neoplasms / Q000098:blood supply* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D003287:Contrast Media; D004164:Diphosphonates / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods*; D011758:Pyrroles / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D011923:Rats, Nude; D000077210:Sunitinib; D023041:Xenograft Model Antitumor Assays; D000077211:Zoledronic Acid
D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D004164:Diphosphonates; D007093:Imidazoles; D007211:Indoles; D011758:Pyrroles; D000077211:Zoledronic Acid; D000077210:Sunitinib