In vitro and in vivo characterization of a new somatostatin (SST) DOTA-conjugated analog

Objectives New SST-analogs with different receptor affinity are being developed to overcome low therapeutic efficacy due to SSTR-selectivity.We evaluated the pharmacological properties of a new SST-analog (Peptide 1) having the same sequence of octreotide, but without the disulphide bridge.

Methods DOTA-Peptide 1 retained optimal affinity profile for SSTR2.The ¹⁷⁷Lu-DOTA-Peptide1 was tested both in vitro,on HEK293-hSSTR2 cells and in vivo in tumor xenograft-bearing nude mice.

Results ¹⁷⁷Lu-DOTA-Peptide 1 was prepared with 98%-100% radiochemical purity, and was stable in serum up to 6 d of incubation.Uptake of ¹⁷⁷Lu-DOTA-Peptide1 by HEK-hSSTR2 cells exhibited a time-dependent pattern, with high internalization at 4-24 hrs.At 4 hr cells retained >50% of the internalized ¹⁷⁷Lu-DOTA-Peptide 1 (Tab 1).Biodistribution:high radioligand uptake in tumors plateauing at 1-4 hr p.i. (22.69±5.36 and 23.69±1.74 %ID/g).Tumor uptake was blocked by about 80% when co-injecting eccess cold DOTA-Peptide-1.Except for the kidneys (6.69±0.70%ID/g),at 24 hr radioactivity cleared from all non-tumor,non-SSTR2-positive tissues, while tumor uptake remained at about 12% ID/g.

Conclusions The ¹⁷⁷Lu-DOTA-Peptide 1 shows promising tumor-targeting properties for diagnostic and therapeutic applications of tumors specifically expressing SSTR2.

Research Support Work supported by COST-STSM-BM0607-04045