Journal
ADVANCED THERAPEUTICS
Volume 4, Issue 4, Pages -Publisher
WILEY
DOI: 10.1002/adtp.202000244
Keywords
glioblastoma; molecular targeting; peptides; PET imaging
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [400975596]
- Sperling Family Foundation
- Harvard Neuro-Discovery Center
- DoD [W81XWH1910791]
- National Science Foundation Graduate Research Fellowship [1122374]
- BWH Innovator Award
- B*CURED Foundation
- NSERC
- BWH Women's Brain Initiative
- BWH Connors Center
- Brigham Research Institute
- [NCI R01CA237063]
- [RO1CA166172]
- U.S. Department of Defense (DOD) [W81XWH1910791] Funding Source: U.S. Department of Defense (DOD)
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Research has identified dg-Bcan as an attractive molecular target for GBM, with the screened BTP-7 peptide showing high affinity and specificity in binding to dg-Bcan. BTP-7 has potential to be further developed into novel imaging agents and targeted therapeutics for GBM.
Glioblastoma (GBM) is the most common and deadliest form of brain tumor and remains amongst the most difficult cancers to treat. Brevican (Bcan), a central nervous system (CNS)-specific extracellular matrix protein, is upregulated in high-grade glioma cells, including GBM. A Bcan isoform lacking most glycosylation, dg-Bcan, is found only in GBM tissues. Here, dg-Bcan is explored as a molecular target for GBM. In this study, a d-peptide library is screened to identify a small 8-amino acid dg-Bcan-Targeting Peptide (BTP) candidate, called BTP-7 that binds dg-Bcan with high affinity and specificity. BTP-7 is preferentially internalized by dg-Bcan-expressing patient-derived GBM cells. To demonstrate GBM targeting, BTP-7 is radiolabeled with F-18, a radioisotope of fluorine, and increased radiotracer accumulation is found in intracranial GBM established in mice using positron emission tomography (PET) imaging. dg-Bcan is an attractive molecular target for GBM, and BTP-7 represents a promising lead candidate for further development into novel imaging agents and targeted therapeutics.
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