In vivo Evaluation of an Engineered Cyclotide as Specific CXCR4 Imaging Reagent.
Chemistry
; 23(58): 14469-14475, 2017 Oct 17.
Article
in En
| MEDLINE
| ID: mdl-28771849
ABSTRACT
The CXCR4 chemokine receptor plays a key regulatory role in many biological functions, including embryonic development and controlling leukocyte functions during inflammation and immunity. CXCR4 has been also associated with multiple types of cancers where its overexpression/activation promotes metastasis, angiogenesis, and tumor growth and/or survival. Furthermore, CXCR4 is involved in HIV replication, as it is a co-receptor for viral entry into host cells. Altogether, these features make CXCR4 a very attractive target for the development of imaging and therapeutic agents. Here, the in vivo evaluation of the MCoTI-based cyclotide, MCo-CVX-5c, for the development of imaging agents that target CXCR4 is reported. Cyclotide MCo-CVX-5c is a potent CXCR4 antagonist with a remarkable in vivo resistance to biological degradation in serum. A [64 Cu]-DOTA-labeled version of this cyclotide demonstrated high and significant uptake in U87-stb-CXCR4 tumors compared to the control U87 tumors. Furthermore, protracted imaging studies demonstrated radiotracer retention in the U87-stb-CXCR4 tumor at 24â
h post injection. Uptake in U87-stb-CXCR4 tumors could be blocked by unlabeled MCo-CVX-5c, showing high in vivo specificity. These results demonstrate the in vivo specificity and retention of a bioactive molecularly targeted cyclotide and highlight the potential of bioactive cyclotides for the development of new imaging agents that target CXCR4.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Contrast Media
/
Receptors, CXCR4
/
Cyclotides
Type of study:
Diagnostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Chemistry
Journal subject:
QUIMICA
Year:
2017
Document type:
Article
Affiliation country:
United States