Comparative small animal SPECT/CT imaging of twelve ¹¹¹In-labelled CCK2-receptor targeting peptides

Objectives CCK2/gastrin receptor targeting using radiolabelled peptides has been investigated in various animal models with a view to using them for diagnosis and therapy of CCK2-R expressing cancers such as MTC and SSLC. The aim of this study was to compare twelve such labelled analogues contributed by six different European centres using small animal SPECT/CT imaging and to rank them on the basis of their tumour targeting properties and clearance from normal tissues.

Methods DOTA-conjugated minigastrin/CCK peptide analogues G-CCK8, SA106, MG0, Sargastrin, MG11, APH070, PP-F10, PP-F6, PP-F16, PP-F11, cyclo-MG1 and MGD5 were radiolabelled with In-111 to a specific activity of 30 MBq/nmol. Beige SCID mice bearing both A431-CCK2 receptor positive and A431-CCK2 receptor negative tumours were injected and imaged at 1 and 4 h. Whole body SPECT images were obtained for 45 minutes, using a four-head scanner with 2 mm pinhole collimators in helical scanning mode and CT images with a 45-kVP X-ray source. Receptor positive and negative tumour uptake as well as kidney uptake was quantified using volume of interest (VOI) analysis of the reconstructed images.

Results Preferential uptake in the CCK2-R expressing tumours was seen for all of the radiopeptides tested. SPECT quantitation of tumour and kidney uptake and retention allowed the peptides to be ranked and this ranking agreed with a low dose biodistribution study carried out in parallel by COST BM0607 study collaborators i.e. the four compounds which appear to be the most promising for therapeutic application are cyclo-MG1, PP-F11, PP-F16 and MGD5.

Conclusions If specific activity can be kept uniform across the panel of compounds, VOI analysis of SPECT imaging data is a useful technique for screening a large number of compounds with a substantial reduction in animal numbers.

Research Support This work was part of COST action BM0607 within Framework 7 of the European Union