Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin

Citation
S. Demartis et al., Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin, EUR J NUCL, 28(4), 2001, pp. 534-539
Citations number
17
Categorie Soggetti
Radiology ,Nuclear Medicine & Imaging","Medical Research Diagnosis & Treatment
Journal title
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
ISSN journal
03406997 → ACNP
Volume
28
Issue
4
Year of publication
2001
Pages
534 - 539
Database
ISI
SICI code
0340-6997(200104)28:4<534:STOTNB>2.0.ZU;2-Q
Abstract
Angiogenesis is a characteristic feature of many aggressive tumours and oth er disorders. Antibodies capable of binding to new blood vessels, but not t o mature vessels, could be used as selective targeting agents for immunosci ntigraphic and radioimmunotherapeutic applications. Here we show that scFv( L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably la belled with iodine-125 and astatine-211 with full retention of immunoreacti vity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistri bution studies in mice bearing two different types of tumour grafted subcut aneously, followed by ex vivo micro-autoradiographic analysis, revealed tha t scFv(L19) rapidly localises around tumour blood vessels, but not around n ormal vessels. Four hours after intravenous injection of the stably radioio dinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 m urine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expect ed, all other organs (including kidney) contained significantly less radioa ctivity than the tumour. Since the ED-B domain of fibronectin has an identi cal sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it sh ould now be possible to investigate scFv(L19) for the selective delivery of At-211 to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse.