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Astatine-211 labelled a small molecule peptide: specific cell killing in vitro and targeted therapy in a nude-mouse model
- Source :
- Radiochimica Acta. 109:119-126
- Publication Year :
- 2020
- Publisher :
- Walter de Gruyter GmbH, 2020.
-
Abstract
- Extensive interest in the development of α-emitting radionuclides astatine-211 (211At) stems from the potential superiority for the treatment of smaller tumors, disseminated disease, and metastatic disease. VP2, a small molecule fusion peptide, can specifically bind to the VPAC1 receptor which is over-expressed in malignant epithelial tumors. In our recent study, we performed the preparation of 211At labelled VP2 through a one-step method. In this work, we explored the targeted radionuclide therapy with [211At]At-SPC-VP2 in vitro and in vivo. The cytotoxicity and specific cell killing of [211At]At-SPC-VP2 were evaluated using the CCK-8 assay. Compared with the [211At]NaAt, the VPAC1-targeted radionuclide compound [211At]At-SPC-VP2 showed more effective cytotoxicity in vitro. Targeted radioactive therapy trial was carried out in non-small-cell lung cancer (NSCLC) xenograft mice. For the therapy experiment, 4 groups of mice were injected via the tail vein with 370 kBq, 550 kBq, 740 kBq, 3 × ∼246 kBq of [211At]At-SPC-VP2, of which the second and third injections were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with saline or 550 kBq [211At]NaAt. The body weight and tumor size of mice were monitored before the administration and every 2 days thereafter. Cytotoxic radiation of partial tissue samples such as kidneys, liver and stomach of mice were assessed by immunohistochemical examination. The tumor growth was inhibited and significantly improved survival was achieved in mice treated with [211At]At-SPC-VP2, two-fold prolongation of survival compared with the control group, which received normal saline or 550 kBq [211At]NaAt. No renal or hepatic toxicity was observed in the mice receiving [211At]At-SPC-VP2, but gastric pathological sections showed 211At uptake in stomach resulting in later toxicity, highlighting the importance of further enhancing the stability of labelled compounds.
- Subjects :
- Cell specific
chemistry.chemical_classification
biology
Chemistry
medicine.medical_treatment
Peptide
biology.organism_classification
Small molecule
In vitro
030218 nuclear medicine & medical imaging
Targeted therapy
Cell biology
03 medical and health sciences
0302 clinical medicine
Cell killing
Nude mouse
In vivo
030220 oncology & carcinogenesis
medicine
Physical and Theoretical Chemistry
Subjects
Details
- ISSN :
- 21933405 and 00338230
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Radiochimica Acta
- Accession number :
- edsair.doi...........6becab18ae60bddbed6076ab3b75a004