1 research outputs found
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 DOTAcoupled
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 68Ga-NeoBOMB1 and 177Lu-
NeoBOMB1. Methods: PC-3 tumor–xenografted BALB/c nu/nu mice
were injected with either approximately 13 MBq/250 pmol 68Ga-
NeoBOMB1 or a low (;1MBq/200pmol) versus high (;1MBq/10 pmol)
peptide amount of 177Lu-NeoBOMB1, after which biodistribution
and imaging studies were performed. At 6 time points (15, 30, 60,
120, 240, and 360 min for 68Ga-NeoBOMB1 and 1, 4, 24, 48, 96,
and 168 h for 177Lu-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. Results: Injection of approximately
250 pmol 68Ga-NeoBOMB1 resulted in a tumor and pancreas
uptake of 12.4 6 2.3 and 22.7 6 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 6 3.3 vs. 11.6 6 1.3 %ID/g of tissue at 240 min after
injection) and a lower pancreatic uptake (19.8 6 6.9 vs. 105 6 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 0.06mGy/MBq, respectively. Imaging studies resulted
in good visualization of the tumor with both 68Ga-NeoBOMB1 and
177Lu-NeoBOMB1. Conclusion: Our findings indicate that 68Ga- or
177Lu-labeled NeoBOMB1 is a promising radiotracer with excellent tumor
uptake and favorable pharmacokinetics for imaging and therapy
of GRPR-expressing tumors