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Saturday, 09/15/2012 5:57:30 AM

Saturday, September 15, 2012 5:57:30 AM

Post# of 346050
I have been reading up on the imaging potential. Trying to connect a few dots.
This paper came out last year. It used a near-infrared (NIR) dye conjugated to the F(ab)2 fragment of PGN635,
now called PGN650, to image PS exposed in mouse glioma.
Near-infrared Optical Imaging of Exposed Phosphatidylserine in a Mouse Glioma Model.
Zhao D, Stafford JH, Zhou H, Thorpe PE.
FREE: http://www.ncbi.nlm.nih.gov/pubmed/22191000

This paper just came out. It shows how NIR imaging used during surgery can be used to detect residual
tumor at the margins of the wound. They use a non-specific NIR dye called ICG to detect the tumor cells.
Intraoperative Near-Infrared Imaging of Surgical Wounds after Tumor Resections Can Detect Residual Disease
Brian Madajewski, Brendan Judy, Anas Mouchli, Veena Kapoor, David Holt, May D. Wang, Shuming Nie, and Sunil Singhal
http://clincancerres.aacrjournals.org/content/early/2012/08/29/1078-0432.CCR-12-1188.abstract

Note that three of the above authors were also on the next paper which came out earlier this year,
with Thorpe as a co-author. Here they used bavi with surgery to prevent relapses from residual tumor cells.
Vascular endothelial-targeted therapy combined with cytotoxic chemotherapy induces inflammatory
intratumoral infiltrates and inhibits tumor relapses after surgery
.
Judy BF, Aliperti LA, Predina JD, Levine D, Kapoor V, Thorpe PE, Albelda SM, Singhal S.
FREE: http://www.ncbi.nlm.nih.gov/pubmed/22577350

Now put the pieces together. You use NIR-PGN650, instead of ICG, specific for PS on tumor vasculature,
to detect the residual tumor real-time during the surgery to remove all the tumor. The PS will be upregulated
if radiation is used first on the tumor. So this is the idea. The timing is such that at the time of surgery there
will be maximum signal to noise ratio for imaging the tumor.
1) Use radiation on the tumor 48 hours before surgery
2) Inject NIR-PGN650 24 hours before surgery
3) During surgery use the NIR real-time detection system as shown in the second paper above to get
all the tumor which will be fluorescent with the NIR-PGN650 bound to all the tumor vasculature and the tumor cells.

This is a video showing how it is done, but here they are using ICG. ICG can not be conjugated to antibodies
because of its structure. The dye used in paper one above, IRDye800CW is made by Li-COR.
http://www.jove.com/video/2225/multispectral-real-time-fluorescence-imaging-for-intraoperative?id=2225
Here is a video about using 800CW in image-guided surgery.
http://www.licor.com/translational/index.jsp
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