Abstract
1686
Objectives Somatostatin receptors (sst1-sst5) are expressed on many neuroendocrine tumors. By default, many patients are studied with 68Ga-DOTA-TOC or 68Ga-DOTA-TATE targeting sst2. Analogs with affinity to more receptor subtypes, such as 68Ga-DOTA-NOC, may image a broader spectrum of tumors or increase the tumor uptake, as several receptor subtypes are present on the same tumor cell. We aim to develop a new 68Ga-labeled PET imaging probe based on SOM230 (Pasireotide), with high affinity for sst1, 2, 3 and 5, for clinical application.
Methods SOM230 was conjugated to DOTA and labeled with 68Ga. The affinity profile of 68Ga-DOTA-SOM230 was evaluated along with internalization studies. Biodistribution and PET imaging were performed in human sst2- and sst5-tumor xenografts. Side-by-side comparison was performed with the clinically used tracers 68Ga-DOTA-TATE and 68Ga-DOTA-NOC.
Results 68Ga-DOTA-SOM230 (SOMscan) exhibited in vitro binding and internalization profiles comparable to SOM230. High and specific tumor uptake was found in hsst2- and hsst5-tumors (14.1±4.5 and 11.4±1.3 %IA/g, respectively, P>0.05), 1h p.i. which remained high at 2h (12.5±3.5 and 7.8±1.2 %IA/g, respectively). 68Ga-DOTA-SOM230 has insignificantly lower uptake in hsst2 than 68Ga-DOTA-TATE (14.1±4.5 and 17.8±2.2 %IA/g, respectively, P>0.05) but much higher in hsst5 (11.4±1.3 and 0.5±0.04 %IA/g, respectively). 68Ga-DOTA-SOM230 had statistically significant higher uptake in hsst5 than 68Ga-DOTA-NOC (11.4±1.3 and 7.7±1.5 %IA/g, respectively, P<0.05), 1h p.i. and similar tumor-to-non tumor ratios. PET images with SOMscan clearly visualized hsst2- and hsst5- tumors 1h p.i. with improved image contrast at 2h.
Conclusions The initial evaluation of 68Ga-DOTA-SOM230 (SOMscan®) reveals its potentiality as PET probe for in vivo imaging of a broad spectrum of somatostatin receptors.
Research Support OctreoPharm Sciences Gmb