Novel target for peptide-based imaging and treatment of brain tumors.
Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas.
Authors' Affiliations: Research Programs Unit, Translational Cancer Biology and Institute of Biomedicine and Laboratory of Molecular Oncology, Biomedicum Helsinki, University of Helsinki; Department of Oncology, Helsinki University Central Hospital; Finnish Cancer Institute, Helsinki; A.I. Virtanen Institute for Molecular Medicine, University of Eastern Finland, Kuopio, Finland; Department of Neurochemistry, Stockholm University, Stockholm, Sweden; and UCSF Helen Diller Family Cancer Center, San Francisco, California.
Maija
M
Hyvönen
Juulia
J
Enbäck
Tuulia
T
Huhtala
Johanna
J
Lammi
Harri
H
Sihto
Janne
J
Weisell
Heikki
H
Joensuu
Katri
K
Rosenthal-Aizman
Samir
S
El-Andaloussi
Ulo
U
Langel
Ale
A
Närvänen
Gabriele
G
Bergers
Pirjo
P
Laakkonen
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007204:Indium / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D060787:Neoplasm Grading; D009374:Neoplasms, Experimental; D009928:Organ Specificity; D010455:Peptides / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000627:therapeutic use; D051381:Rats; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D050556:Fatty Acid-Binding Proteins; D010455:Peptides; D007204:Indium; C020758:indium trichloride