Among various newly synthesized chelator-linked octreotide analogues Y-90-[
DOTA-DPhe(1), Thyr(3)]-octreotide (Y-90-SMT 487) was finally selected for c
linical development. In vitro, SMT 487 binds selectively with nanomolar aff
inity to the somatostatin receptor subtype 2 (IC30 = 0.39 nM +/- 0.02). In
vivo, Y-90-[DOTA-DPhe(1), Thyr(3)]-octreotide shows a rapid blood clearance
(T-1/2 alpha<5 min) and high accumulation in somatostatin subtype 2 recept
or expressing tumours. The in vivo administration of Y-90-[DOTA-DPhe(1), Th
yr(3)]-octreotide induces a rapid tumour shrinkage in three different somat
ostatin receptor positive tumour models: CA20948 rat pancreatic rumours gro
wn in normal rats, AR42J mt pancreatic tumours and NCI-H69 human small cell
lung cancer both grown in nude mice. The radiotherapeutic efficacy of Y-90
-SMT 487 was enhanced in combination with standard anticancer drugs, such a
s mitomycin C, which resulted in a tumour decrease of 70% of the initial vo
lume. In the CA 20948 syngeneic rat tumour model, a single treatment with 1
0 mu Ci/kg Y-90-SMT 487 resulted in the disappearance of 5 out of 7 tumours
. Thus the new radiotherapeutic agent showed its curative potential for the
selective treatment of SRIF receptor-expression tumours. Clinical Phase I
studies with Y-90-SMT 487 were started in September 1997.