MR maps tumor angiogenesis with targeted nanoparticles
Effective imaging of the formation of new blood vessels feeding invasive tumors is essential to the continued development of antiangiogenetic therapy. A range of imaging methods and antiangiogenic drugs have been developed in this area with inconsistent results, but a technique using 3D MR and avb3-receptor targeted nanoparticles is providing an index of new vessel development over time that could push research forward and potentially improve patient management and outcomes of antiangiogenetic therapy, according to a study published online June 14 in Radiology.
Anne H. Schmieder, MS, from the department of medicine at Washington University Medical School in St Louis, Mo., and colleagues mapped longitudinal angiogenesis across differing treatments in rabbits with implanted Vx2 cancer cells using 3D MR with T1-weighted gradient-echo pulse sequences on a 3T system to compare the effectiveness of Gd-DOTA-PE and Gd-DTPA-BOA PFC paramagmetic nanoparticles for the assessment of tumor angiogenesis.
Antiangiogenic therapy could be considered a fourth line of treatment for cancer and a supplement to radiation therapy chemotherapy and surgery, but improvements in efficacy and evaluation are needed.
“Unfortunately, antiangiogenic agents, even in combination with traditional chemotherapy, have met with variable success, with effectiveness often observed only in certain subgroups of patients,” wrote Schmieder et al. “Clearly, an unmet need persists to risk stratify patients for adjunctive angiogenic therapy and to better manage the timing and dosing of such treatments for maximum benefit. The ability to assess and possibly predict the efficacy of novel antiangiogenic cancer therapies could greatly increase the benefit-risk ratio for candidate patients.”
Techniques currently used to track neovascularity involve perfusion imaging of microvessel density with CT and dynamic contrast material–enhanced MR, but these have not been sufficient to show absolute antiangiogenic response.
“In particular, neovascularity estimates obtained with blood pool contrast diffusion pharmacokinetics have been shown to differ greatly from results obtained with integrin-targeted paramagnetic nanoparticles,” wrote the authors.
Out of various modalities, including PET/CT, photoacoustic tomography and contrast enhanced ultrasonography, MR is pooling the best results.
“Of these modalities, MR imaging offers the distinct advantage of high-spatial-resolution imaging without ionizing radiation, as well as the ability to noninvasively probe shallow and deep tumors,” the researchers wrote.
For this research, a total of 26 models were studied in three separate investigations involving with either Gd-DTPA-BOA or Gd-DOTA-PE or nontargeted nanoparticles. Contrast-enhanced MR images were acquired three hours after injection.
Results showed that MR signal intensity enhancement of the neovascular activation was superior with tetraazacyclododecane tetraacetic acid phosphatidylethanolamine nanoparticles with higher relaxitivity. These carried the gadolinium contrast through the lipid layer, unlike the diethylenetrianime pentaacedic acid bisoleate nanoparticles that deposited gadolinium approximately at the water-particle interface.
“In our present study, we demonstrated consistent time-dependent expansion of the neovascular index over time on an individual basis with avb3-targeted Gd-DOTA-PE nanoparticles; this finding was not observed with the nontargeted paramagnetic nanoparticles,” wrote the authors.
At 14 days, neovascular contrast enhancement was assessed at about 5.4 percent surface volume of the models’ Vx2 tumors with avb3-targeted Gd-DOTA-PE nanoparticles and about 3 percent for similarly targeted Gd-DTPA-BOA nanoparticles (P = .03). MR angiogenetic mapping of tumors showed steady contrast enhancement with at about 1 percent after 8 days, 4.5 percent at 14 days and 9.3 percent at 16 days after implantation (P = .0008).
“Neovascular mapping and indexes may provide sensitive metrics with which to detect and characterize vascular expansion in nascent proliferating solid tumors, which could be useful to risk stratify antiangiogenesis treatment in patients with cancer or to follow therapeutic responses longitudinally,” the authors wrote.