Biomedical Engineering Reference
In-Depth Information
fragments and affibody molecules, in place of whole antibodies [
38
]. Alternatively,
overexpression of specific cell-surface receptors by certain tumors can be exploited
using radiolabelled peptides.
28.3.2
Peptide-receptor radionuclide therapy
Radiolabelled peptides have been studied extensively for use in radionuclide
therapy. This is due to their excellent binding efficiencies, selectivity, and fa-
vorable pharmacokinetic characteristics Tumor targeting with peptides has found
both diagnostic and therapeutic applications. In the case of cancer diagnosis and
radiotherapy, a radioligand is usually attached to the regulatory peptide carrier by
the aid of a chelator. A wide variety of chelating agents (e.g., diethylenetriamine-
pentaacetic acid [DTPA] and 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic
acid [DOTA]) have been developed for convenient radiolabeling of peptides. The
most studied peptides for peptide-receptor radionuclide therapy (PPRT) are the
radiolabeled somatostatin analogs. Apart from somatostatin analogs, many other
peptides have been developed for PRRT, including cholecystokinin-2/gastrin re-
ceptors (CCK-2r), gastrin-releasing peptide receptors (GRP-r), vasoactive intestinal
peptide receptors-1 (VPAC1-r), melanocortin-1 receptors (MCR-1r), neurotensin
receptors-1 (NTR-1), neuropeptide Y-Y1 receptors (NP-Y Y1r),
integrins,
gonadotropin-releasing hormone receptors (GnRHr-I), and glucagon-like peptide-1
receptors (GLP-1r). These receptors are overexpressed on various tumor types and
can be targeted with peptide analogs with high affinity [
80
].
'“3
28.3.2.1
Somatostatin Targeting
Somatostatin (SMS), is a naturally occurring cyclic 14- or 28-amino acid peptide
[
81
,
82
] which binds to the somatostatin receptors-SSTRs (sst
1
;
sst
4
,
and sst
5
). SSTRs are expressed in most gastroenteropancreatic neuroendocrine
tumors (GEPNETs) as well as in some other malignancies including breast cancer,
neuroblastoma, and lymphomas [
14
,
83
]. This renders SSTRs as ideal targets
for peptide-receptor radionuclide therapy (PRRT). However, few Auger emitter
complexes for PRRT have been tested in clinical trials.
111
In- DTPA-derivatised octreotide (Octreoscan
R
ss
t2
, sst
3
;
, Covidien, Hazelwood, MO)
was developed in the late 1980s for the diagnostic imaging of somatostatin
.
sst
2
/
-photon emissions of
111
In;
171 keV (90%) and 245 keV (94%) [
84
] Since then it has been used for PRRT
exploiting the Auger electron emissions, rather than the
overexpressing tumors taking advantage of the two
”
-emissions used for tumor
imaging [
85
-
89
] Although in vitro experiments with
111
In-DTPA-octreotide noted
a therapeutic effect dependent on the internalization ability of the complex [
90
],
limited clinical success has been noted. The lower efficacy reported in larger tumors
is most likely related to the limited range of Auger electrons [
91
], as the decay of
”
