68Ga/177Lu-NeoBOMB1, A Novel Radiolabeled GRPR Antagonist For Theranostic Use In Oncology

Since overexpression of the gastrin releasing peptide receptor (GRPR) has been reported on various cancer types, e.g. prostate cancer and breast cancer, targeting this receptor with radioligands might have significant impact on staging and treatment of GRPR-expressing tumors. NeoBOMB1 is a novel DOTA-coupled GRPR antagonist with high affinity for GRPR and excellent in vivo stability. The purpose of this preclinical study was to further explore the use of NeoBOMB1 for theranostic application by determining the biodistribution of (68)Ga-NeoBOMB1 and (177)Lu-NeoBOMB1.

PC-3 tumor-xenografted Balb c nu/nu mice were injected with either ~13 MBq/250 pmol (68)Ga-NeoBOMB1, or a low (~1 MBq/200 pmol) vs. high (~1 MBq/10 pmol) peptide amount of (177)Lu-NeoBOMB1 after which biodistribution and imaging studies were performed. At 6 time points (15, 30, 60, 2 h, 4 h and 6 h for (68)Ga-NeoBOMB1 and 1, 4, 24, 48, 96 and 168 h for (177)Lu-NeoBOMB1) post injection (p.i.) tumor and organ uptake was determined. To assess receptor-specificity additional groups of animals were co-injected with an excess of unlabeled NeoBOMB1. Results of the biodistribution studies were used to determine pharmacokinetics and dosimetry. Furthermore, positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/magnetic resonance imaging (SPECT/MRI) was performed.

Injection of ~250 pmol (68)Ga-NeoBOMB1 resulted in a tumor and pancreas uptake of 12.4±2.3 and 22.7±3.3 %ID/g tissue 120 min p.i., respectively. (177)Lu-NeoBOMB1 biodistribution studies revealed a higher tumor uptake (17.9±3.3 vs. 11.6±1.3 %ID/g tissue 4 h p.i.) and a lower pancreatic uptake (19.8±6.9 vs. 105±13 %ID/g tissue 4 h p.i.) with the higher peptide amount injected, leading to a significant increase in the absorbed dose to the tumor vs. the pancreas (200 pmol: 570 vs. 265 mGy/MBq, 10 pmol: 435 vs. 1393 mGy/MBq). Using this data to predict patient dosimetry we found a kidney, pancreas and liver exposure of 0.10, 0.65 and 0.06 mGy/MBq, respectively. Imaging studies resulted in good visualization of the tumor with both (68)Ga-NeoBOMB1 and (177)Lu-NeoBOMB1.

Our findings indicate that (68)Ga/(177)Lu-NeoBOMB1 is a very promising radiotracer with excellent tumor uptake and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Sep 08 [Epub ahead of print]

Simone U Dalm, Ingrid L Bakker, Erik de Blois, Gabriela N Doeswijk, Mark W Konijnenberg, Francesca Orlandi, Donato Barbato, Mattia Tedesco, Theodosia Maina, Berthold A Nock, Marion de Jong

Erasmus MC, Netherlands;, Advanced Accelerator Applications, Italy;, INSRATES, NCSR, Greece.