68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology.
Because overexpression of the gastrin-releasing peptide receptor (GRPR) has been reported on various cancer types, for example, prostate cancer and breast cancer, targeting this receptor with radioligands might have a 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 of68Ga-NeoBOMB1 and177Lu-NeoBOMB1.



PC-3 tumor-xenografted BALB/c nu/nu mice were injected with either approximately 13 MBq/250 pmol68Ga-NeoBOMB1 or a low (∼1 MBq/200 pmol) versus high (∼1 MBq/10 pmol) peptide amount of177Lu-NeoBOMB1, after which biodistribution and imaging studies were performed. At 6 time points (15, 30, 60, 120, 240, and 360 min for68Ga-NeoBOMB1 and 1, 4, 24, 48, 96, and 168 h for177Lu-NeoBOMB1) postinjection tumor and organ uptake was determined. To assess receptor specificity, additional groups of animals were coinjected with an excess of unlabeled NeoBOMB1. Results of the biodistribution studies were used to determine pharmacokinetics and dosimetry. Furthermore, PET/CT and SPECT/MRI were performed.



Injection of approximately 250 pmol68Ga-NeoBOMB1 resulted in a tumor and pancreas uptake of 12.4 ± 2.3 and 22.7 ± 3.3 percentage injected dose per gram (%ID/g) of tissue, respectively, at 120 min after injection.177Lu-NeoBOMB1 biodistribution studies revealed a higher tumor uptake (17.9 ± 3.3 vs. 11.6 ± 1.3 %ID/g of tissue at 240 min after injection) and a lower pancreatic uptake (19.8 ± 6.9 vs. 105 ± 13 %ID/g of tissue at 240 min after injection) with the higher peptide amount injected, leading to a significant increase in the absorbed dose to the tumor versus the pancreas (200 pmol, 570 vs. 265 mGy/MBq; 10 pmol, 435 vs. 1393 mGy/MBq). Using these 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 both68Ga-NeoBOMB1 and177Lu-NeoBOMB1.



Our findings indicate that68Ga- or177Lu-labeled NeoBOMB1 is a promising radiotracer with excellent tumor uptake and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands s.dalm@erasmusmc.nl.
Simone U
SU
Dalm
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Ingrid L
IL
Bakker
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Erik
E
de Blois
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Gabriela N
GN
Doeswijk
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Mark W
MW
Konijnenberg
Advanced Accelerator Applications, Colleretto Giacosa, Italy; and.
Francesca
F
Orlandi
Advanced Accelerator Applications, Colleretto Giacosa, Italy; and.
Donato
D
Barbato
Advanced Accelerator Applications, Colleretto Giacosa, Italy; and.
Mattia
M
Tedesco
Molecular Radiopharmacy, INRASTES, NCSR "Demokritos", Athens, Greece.
Theodosia
T
Maina
Molecular Radiopharmacy, INRASTES, NCSR "Demokritos", Athens, Greece.
Berthold A
BA
Nock
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Marion
M
de Jong
D000818:Animals; D001839:Bombesin / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005710:Gallium Radioisotopes / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000627:therapeutic use; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D016896:Treatment Outcome
D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D001839:Bombesin
GRPR antagonist; biodistribution; cancer theranostics; dosimetry; gastrin releasing peptide receptor