RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 583
OP 583
VO 57
IS supplement 2
A1 Berthold Nock
A1 Aikaterini Kaloudi
A1 Emmanouil Lymperis
A1 Athina Giarika
A1 Hendrik Bergsma
A1 Dirk Mueller
A1 Eric Krenning
A1 Marion de Jong
A1 Theodosia Maina
A1 Richard Baum
YR 2016
UL http://jnm.snmjournals.org/content/57/supplement_2/583.abstract
AB 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.