Targeting small-cell lung cancer with novel fluorescent analogs of somatostatin.
Early, accurate detection of small-cell lung cancer (SCLC), before it becomes systemic, is essential for successful treatment. Fluorescence-based imaging provides safe, sensitive detection of malignancies. Targeted delivery of fluorophores increases sensitivity of endoscopic imaging. We synthesized novel somatostatin analogs, based on backbone cyclic peptides, and conjugated them with fluorescent agents. Nineteen conjugates differing in core peptide, length of alkyl linker and fluorescence moiety (rhodamine and fluorescein) were tested in vitro, using a receptor binding assay, and nine of the more promising conjugates were tested in vivo by fiber-optic spectrofluorimetry and quantitative spectral imaging, on an H69 human SCLC tumor mouse xenograft model. The lead compound showed exceptional tumor/normal tissue ratios, ranging from 9 to 90, and has potential for targeting SCLC overexpressing somatostatin receptors.
Kostenich
Genady
G
Advanced Technology Center, Sheba Medical Center, Tel Hashomer 52621, Israel. genakos@sheba.health.co.il
Livnah
Nurit
N
Bonasera
Thomas A
TA
Yechezkel
Tamar
T
Salitra
Yosef
Y
Litman
Pninit
P
Kimel
Sol
S
Orenstein
Arie
A
D000595:Amino Acid Sequence; D000818:Animals; D018288:Carcinoma, Small Cell / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D008175:Lung Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011869:Radioligand Assay; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence / Q000379:methods; D014183:Transplantation, Heterologous
D005456:Fluorescent Dyes; D017481:Receptors, Somatostatin; D013004:Somatostatin; C093733:somatostatin receptor 2