TY - JOUR T1 - [68Ga]NeoBomb1, a new potent GRPR-antagonist for PET imaging - Preclinical and first clinical evaluation in prostate cancer JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 583 LP - 583 VL - 57 IS - supplement 2 AU - Berthold Nock AU - Aikaterini Kaloudi AU - Emmanouil Lymperis AU - Athina Giarika AU - Hendrik Bergsma AU - Dirk Mueller AU - Eric Krenning AU - Marion de Jong AU - Theodosia Maina AU - Richard Baum Y1 - 2016/05/01 UR - http://jnm.snmjournals.org/content/57/supplement_2/583.abstract N2 - 583Objectives We have recently reported on [68Ga]SB3 ([68Ga-DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), a high affinity GRPR (gastrin releasing peptide receptor)-antagonist displaying high in vivo targeting of human PC-3 xenografts in mice and promising diagnostic profile in patients with prostate (PC) and breast cancer (BC). We herein present the potent GRPR-antagonist [68Ga]NeoBomb1 generated by proper modification of the C-terminal Leu-NHEt part and its preclinical profile in GRPR-expressing cells and mouse models. First evidence of its ability to localize PC-lesions in man is also presented.Methods The affinity of NeoBomb1 and [natGa]NeoBomb1 for the GRPR was determined against [125I-Tyr4]BBN in PC-3 cell membranes and the binding of [67Ga]NeoBomb1 to PC-3 cells was studied at 37oC. Blood collected 5 min post injection (pi) in mice was analyzed by HPLC for metabolites. Biodistribution was studied in SCID mice bearing PC-3 xenografts at 1 h and 4 h pi (±40 nmol [Tyr4]BBN). PET/CT images with [68Ga]NeoBomb1 were acquired in PC patients.Results NeoBomb1 and [natGa]NeoBomb1 showed high affinity for the GRPR (IC50 ≍ 1 nM), while [67Ga]NeoBomb1 bound strongly on the cell-surface of PC-3 cells via a GRPR-specific process, as consistent with a potent antagonist profile. [67Ga]NeoBomb1 showed excellent metabolic stability in peripheral mouse blood and very high and GRPR-specific uptake in PC-3 xenografts in mice (33.1±8.2%ID/g at 1 h pi and 30.6±3.9%ID/g at 4 h pi). Background activity cleared predominantly via the kidneys. In a first primary PC patient (PSA 10.6 ng/ml, accidental finding at screening and a 3-times false-negative biopsy), [68Ga]NeoBomb1 rapidly localized in the lesion achieving high contrast visualization.Conclusions [68Ga]NeoBomb1 displays high, specific and rapid localization in PC-3 xenografts in mice as well as in a first primary PC patient, revealing the potential of antagonist-based radiotracers to image GRPR-positive cancer with PET. ER -