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
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.