Evaluating the Usefulness of a Novel 10B-Carrier Conjugated With Cyclic RGD Peptide in Boron Neutron Capture Therapy.
World J Oncol
; 3(3): 103-112, 2012 Jun.
Article
en En
| MEDLINE
| ID: mdl-29147290
ABSTRACT
BACKGROUND:
To evaluate the usefulness of a novel 10B-carrier conjugated with an integrin-binding cyclic RGD peptide (GPU-201) in boron neutron capture therapy (BNCT).METHODS:
GPU-201 was synthesized from integrin-binding Arg-Gly-Asp (RGD) consensus sequence of matrix proteins and a 10B cluster 1, 2-dicarba-closo-dodecaborane-10B. Mercaptododecaborate-10B (BSH) dissolved in physiological saline and BSH and GPU-201 dissolved with cyclodextrin (CD) as a solubilizing and dispersing agent were intraperitoneally administered to SCC VII tumor-bearing mice. Then, the 10B concentrations in the tumors and normal tissues were measured by γ-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, then treated with GPU-201, BSH-CD, or BSH. Immediately after reactor neutron beam or γ-ray irradiation, during which intratumor 10B concentrations were kept at levels similar to each other, cells from some tumors were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (= P + Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU.RESULTS:
The 10B from BSH was washed away rapidly in all these tissues and the retention of 10B from BSH-CD and GPU-201 was similar except in blood where the 10B concentration from GPU-201 was higher for longer. GPU-201 showed a significantly stronger radio-sensitizing effect under neutron beam irradiation on both total and Q cell populations than any other 10B-carrier.CONCLUSION:
A novel 10B-carrier conjugated with an integrin-binding RGD peptide (GPU-201) that sensitized tumor cells more markedly than conventional 10B-carriers may be a promising candidate for use in BNCT. However, its toxicity needs to be tested further.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
World J Oncol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Japón