Satoshi G. Harada MD, Presenter: Nothing to Disclose

Shigeru Ehara MD, Abstract Co-Author: Nothing to Disclose

Takahiro Satoh DSc, Abstract Co-Author: Nothing to Disclose

Masashi Koka RT, PhD, Abstract Co-Author: Nothing to Disclose

Koichiro Sera, Abstract Co-Author: Nothing to Disclose

We aimed to image and treat the micrometastases of B16F10 murine melanoma cells in C57/BL6 mice, using microcapsules that release liposome-protamine-hyaluronic acid nanoparticles (LPH-NP) in response to radiation, in three radiation sessions. 

In session one, 5% Iopamiron and CT-detectable microcapsules containing P-selectin and LPH-NP were mixed with 1 mL of a solution of 4% alginate, 3% hyaluronate, 1mg ascorbate, and 1μg/mL P-selectin.  This was sprayed into 0.5 mmol/L FeCl2 containing 1μg/mL α4β1 antibody  (Ab).  Mice were injected intravenously (IV) with microcapsules, then 9 h later exposed to 10 or 20Gy 60Co γ radiation.  In session two, CD47 (the "don't eat me" signal) was knocked down in metastatic cells.  To do this, anti-CD47 siRNA LPH-NP modified with a CD4 scFv Ab were mixed with the above cocktail and sprayed into 0.5 mmol/L FeCl2 containing 1 μg/mL anti-P-selectin Ab.  Microcapsules (1 X 1010) were injected IV and interacted with P-selectin for 9 h to treat micrometastases.  Then, second irradiation was given, which was conducted similar to the first session.   In session three, 4 cGy 60Co whole-body γ radiation was administered at 24-h intervals for 5 days to activate macrophages and CD8+T cells. 

In session one, anti-α4β1 microcapsules accumulated around micrometastatic sites and were detected by CT.  The microcapsules released P-selectin and nanoparticles with Iopamiron in response to the first irradiation.  The nanoparticle were endocytosed, prolonging the detection of micrmetastases.  In session two, anti-P-selectin microcapsules accumulated around micrometastatic sites.  The microcapsules released anti-CD47 siRNA LPH-NP with CD4 scFv Ab in response to seond irradiation, which silenced CD47 in metastatic cells.  The third radiation session activated macrophages and CD8+T cells.  Overall, these treatments resulted in an 82.9% reduction in micrometastases. 

The use of nanoparticles and low-dose whole-body radiation can improve the diagnosis and treatment of micrometastasies. 

The imaging-targeted knockdown of CD47 and the activation of macrophaged and CD8+Tcells may facilitate the improved diagnosis and treatment of micrometastases. 

Harada, S, Ehara, S, Satoh, T, Koka, M, Sera, K, Nanoparticle Imaging and Treatment of Micrometastasis, Using Targeted Anti-CD47 siRNA Nanoparticle, via Radiotherapy.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14003474.html