Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Positron Emission Tomography as a Quantitative Method for the Follow-Up of Neovascularization in Ischemic Tissues
Hakan Orbay, MD, PhD1, Timothy A. Hacker, PhD2, Weibo Cai, PhD2, David E. Sahar, MD1.
1UCDavis, Sacramento, CA, USA, 2UW - Madison, Madison, WI, USA.

PURPOSE: Neovascularization is a crucial process for adequate wound healing. The goal of this study is to evaluate positron emission tomography (PET) for noninvasive and quantitative assessment of neovascularization in ischemic tissues using a mouse hindlimb ischemia model.
METHODS: Hindlimb ischemia was induced by ligation of the right femoral arteries in BALB/c mice under anesthesia, and the left hindlimb served as an internal control. Mice in the treatment group were given intraperitoneal pravastatin daily until the end of the study, whereas the animals in the control group were injected with 0.9% sodium chloride solution. The blood flow in the hindlimbs was measured with laser Doppler imaging before and after the operation and on postoperative days 3, 10, 17, and 24. Neovascularization was non-invasively monitored and quantified with (64)Cu-NOTA-TRC105 PET on postoperative days 3, 10, 17, and 24. Neovascularization in the ischemic hindlimb was further confirmed with immunofluorescence staining.
RESULTS: Laser Doppler imaging showed that blood flow in the ischemic hindlimb plummeted to ~20% of the normal level after surgery, and gradually recovered to near normal level on day 10 in the treatment group and on day 20 in the control group (Fig.1). Tracer uptake at 48 h post-injection in the ischemic hindlimb in the treatment group was significantly higher than that of the control group on day 10 (20.5 ± 1.9 %ID/g vs 11.4 ± 1.5 %ID/g) (Fig.1), suggesting increased CD105 expression and higher level of neovascularization upon pravastatin treatment, and gradually decreased to background levels in both groups (4.9 ± 0.8 %ID/g vs 3.4 ± 1.9 %ID/g on day 24). The in vivo PET data correlated well with ex vivo biodistribution studies performed on day 24.
CONCLUSION: Taken together, our results indicated that (64)Cu-NOTA-TRC105 PET is a suitable and non-invasive method to monitor neovascularization; therefore, it can be a utilized for non-invasive evaluation of the ischemic wounds and / or flap vascularization.


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