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Anticancer activity of targeted proapoptotic peptides
Astrid Capello1, Eric P Krenning, Bert F Bernard
1Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Summary
Hybrid peptides combining RGD and somatostatin show promise for cancer therapy. While RGD-(111)In-DTPA-octreotate has high renal uptake, unlabeled RGD-DTPA-octreotate and RGD-octreotate activate caspase-3, indicating therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Radiochemistry
Background:
- Tumor angiogenesis involves alpha(v)beta(3)-receptors targeted by RGD peptides.
- Somatostatin analogs target somatostatin receptors on tumor cells.
- Hybrid peptides combine RGD and somatostatin for dual targeting.
Purpose of the Study:
- Evaluate biodistributions of RGD-(111)In-DTPA-octreotate and (125)I-RGD-octreotate.
- Investigate in vitro caspase-3 activation by RGD-DTPA-octreotate.
- Assess the therapeutic potential of novel hybrid peptides.
Main Methods:
- Biodistribution studies in tumor-bearing rats using radiolabeled peptides.
- In vitro caspase-3 activation assays (colorimetric and immunocytochemical).
- Affinity measurements using inhibitory concentration (IC50).
Main Results:
- RGD-(111)In-DTPA-octreotate showed high tumor uptake but also significant renal uptake.
- (125)I-RGD-octreotate exhibited lower renal uptake and higher affinity compared to the DTPA-containing analog.
- Unlabeled RGD-DTPA-octreotate and RGD-octreotate significantly increased caspase-3 levels in vitro, indicating apoptosis induction.
Conclusions:
- High renal uptake limits RGD-(111)In-DTPA-octreotate for radionuclide therapy.
- Unlabeled RGD-DTPA-octreotate and RGD-octreotate demonstrate therapeutic potential via caspase-3 activation.
- Development of hybrid molecules represents a novel strategy for cancer treatment.