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Targeted and Selective Treatment of Pluripotent Stem Cell-derived Teratomas Using External Beam Radiation in a Small-animal Model
Published on: February 17, 2019
Antiangiogenic therapy with somatostatin receptor-mediated in situ radiation
S A Gulec1, C M Gaffga, C T Anthony
1The Louisiana State University Health Sciences Center, Department of Surgery, New Orleans 70112, USA.
Abstract:
Tumor growth and the development of metastases require an angiogenic response. Angiogenic vessels uniquely express somatostatin subtype 2 (sst 2) receptors that can transport somatostatin or its analogs into the cell. We hypothesized that radiolabeled somatostatin analogs could inhibit the angiogenic response by selectively destroying proliferating endothelial cells. We evaluated the antiangiogenic effects of 111In-pentetreotide, an sst 2-preferring somatostatin analog in a human vessel model. Disks of human placental vein were embedded in fibrin gels in culture and observed for angiogenic sprouting for 14 days. Vein disks were treated with 111In-pentetreotide (1.5, 15, and 150 microCi/mL) on the day of implantation. Control groups included disks treated with nutrient medium alone, with 111In-chloride, and with unlabeled pentetreotide. The percentage of wells that initiated an angiogenic response and the overall length and density of neovessel sprouts were assessed on Day 14. 111In-pentetreotide treatment did not completely block initiation of the angiogenic response but significantly decreased the growth of neovessels after initiation. Both the receptor-specific Auger electron-induced and nonspecific gamma radiation-mediated effects contributed to the angiotoxicity.
Insights
Radiolabeled somatostatin analogs like 111In-pentetreotide show potential in inhibiting tumor angiogenesis. This study found that these analogs significantly reduced new blood vessel growth in a human vessel model.
Area of Science:
- Oncology
- Radiopharmacology
- Vascular Biology
Background:
- Tumor growth and metastasis depend on angiogenesis, the formation of new blood vessels.
- Angiogenic vessels express somatostatin subtype 2 (sst 2) receptors, enabling targeted delivery of somatostatin analogs.
- Selective destruction of proliferating endothelial cells via targeted agents is a potential anti-cancer strategy.
Purpose of the Study:
- To evaluate the anti-angiogenic effects of 111In-pentetreotide, a somatostatin analog, in a human vessel model.
- To determine if radiolabeled somatostatin analogs can inhibit the angiogenic response by targeting sst 2 receptors on endothelial cells.
- To assess the impact of 111In-pentetreotide on neovascularization and endothelial cell proliferation.
Main Methods:
- Human placental vein explants were cultured in fibrin gels to assess angiogenic sprouting over 14 days.
- Explants were treated with varying concentrations of 111In-pentetreotide (1.5, 15, 150 microCi/mL).
- Control groups included untreated explants, 111In-chloride, and unlabeled pentetreotide; angiogenic response, sprout length, and density were quantified.
Main Results:
- 111In-pentetreotide treatment significantly reduced the growth and density of neovessels after angiogenic initiation.
- The anti-angiogenic effect was observed across different concentrations, indicating a dose-dependent response.
- Both receptor-specific Auger electron effects and non-specific gamma radiation contributed to the observed angiotoxicity.
Conclusions:
- 111In-pentetreotide demonstrates significant anti-angiogenic properties by inhibiting endothelial cell proliferation and neovessel growth.
- The study supports the hypothesis that radiolabeled somatostatin analogs can be utilized to target and damage angiogenic vessels.
- Targeted radionuclide therapy using somatostatin analogs presents a promising approach for anti-angiogenic cancer treatment.
