Evaluation in vivo and ex vivo of a new stabilized 99mTc-labeled minigastrin derivative

1235 Objectives: The development of radiolabeled Minigastrin (MG) derivatives for imaging and therapy of CCK2-receptor expressing tumors such as MTC and SCLC has been hampered by low stability of the native peptide. In this study we describe the evaluation of a new 99mTc-labeled analog stabilized by cyclisation, comparing the organ and tumor uptake in vivo using micro-SPECT/CT imaging with quantification ex vivo. Methods: Cyclisation of MG was achieved by replacing Gly by DLys at Pos 9 allowing cyclisation with DGlu in Pos 1. 99mTc-labelling was carried out by derivatisation with HYNIC at the N-terminal and with EDDA as coligand. Stability and receptor mediated internalization in CCK2-receptor expressing AR4-2J cells were evaluated. Biodistribution was studied in AR4-2J tumor bearing nude mice, including NanoSPECT/CT imaging. Metabolites in urine, liver and kidneys were analyzed by HPLC. Results: Cyclo-MG showed improved radiochemical purity in the labelling process, allowing 99mTc-labelling at high specific activities with high yields. The radioligand revealed high stability in vitro and receptor mediated uptake in AR4-2J cells. In the animal tumor model fast renal clearance and low unspecific uptake in most organs were observed. Tumor uptake 1 h p.i. was 3.26 %ID/g in vivo and 3.61 %ID/g ex vivo. The metabolite analysis indicated rapid conversion into the linear peptide sequence and enzymatic degradation in vivo. Conclusions: Cyclisation of MG only had a limited effect on the stability of radiolabeled MG. Overall biodistribution was comparable to linear analogs. Quantification of the organ and tumor uptake by SPECT/CT image fusion was in accordance with ex vivo data.