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VCAM-1 targeted alpha-particle therapy for early brain metastases
- Source :
- ICRR 2019, ICRR 2019, Aug 2019, Manchester, United Kingdom, 12èmes journées scientifiques du Cancéropôle Nord-Ouest, 12èmes journées scientifiques du Cancéropôle Nord-Ouest, May 2019, Deauville, France, Neuro-Oncology, Neuro-Oncology, Oxford University Press (OUP), 2019, 22 (3), pp.357-368. ⟨10.1093/neuonc/noz169⟩, Brain & Brain Pet 2019, Brain & Brain Pet 2019, Jul 2019, Yokohama, Japan. Journal of cerebral blood flow and metabolism, 39 (PB03-G06), pp.409-409, Neuro-Oncology, 2019, 22 (3), pp.357-368. ⟨10.1093/neuonc/noz169⟩, 4ème Journée Normande de Recherche Biomédicale, JNRB 2019, 4ème Journée Normande de Recherche Biomédicale, JNRB 2019, Nov 2019, Caen, France
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- Background Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1). Methods Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT. Results 212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed. Conclusions The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Mice, Nude
Vascular Cell Adhesion Molecule-1
Breast Neoplasms
Antibodies
Targeted therapy
early brain metastases
Mice
03 medical and health sciences
0302 clinical medicine
Breast cancer
Cell Line, Tumor
Internal medicine
Carcinoma
medicine
AcademicSubjects/MED00300
Animals
Humans
External beam radiotherapy
Stage (cooking)
030304 developmental biology
VCAM-1
0303 health sciences
alpha-particle therapy
Radiotherapy
Brain Neoplasms
business.industry
Brain
Histology
Lead Radioisotopes
Alpha Particles
medicine.disease
3. Good health
Radiation therapy
[SDV] Life Sciences [q-bio]
030220 oncology & carcinogenesis
Basic and Translational Investigations
Toxicity
AcademicSubjects/MED00310
Female
Neurology (clinical)
business
Subjects
Details
- Language :
- English
- ISSN :
- 15228517 and 15235866
- Database :
- OpenAIRE
- Journal :
- ICRR 2019, ICRR 2019, Aug 2019, Manchester, United Kingdom, 12èmes journées scientifiques du Cancéropôle Nord-Ouest, 12èmes journées scientifiques du Cancéropôle Nord-Ouest, May 2019, Deauville, France, Neuro-Oncology, Neuro-Oncology, Oxford University Press (OUP), 2019, 22 (3), pp.357-368. ⟨10.1093/neuonc/noz169⟩, Brain & Brain Pet 2019, Brain & Brain Pet 2019, Jul 2019, Yokohama, Japan. Journal of cerebral blood flow and metabolism, 39 (PB03-G06), pp.409-409, Neuro-Oncology, 2019, 22 (3), pp.357-368. ⟨10.1093/neuonc/noz169⟩, 4ème Journée Normande de Recherche Biomédicale, JNRB 2019, 4ème Journée Normande de Recherche Biomédicale, JNRB 2019, Nov 2019, Caen, France
- Accession number :
- edsair.doi.dedup.....3131861cde96343ba2769b3d1e691987