Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [68Ga]SB3 and PET/CT

Maina, Theodosia; Bergsma, Hendrik; Kulkarni, Harshad; Müeller, Dirk; Charalambidis, David; Krenning, Eric P.; Nock, Berthold A.; Jong, Marion de; Baüm, Richard

doi:10.1007/s00259-015-3232-1

Cited by 96 publications

(148 citation statements)

References 34 publications

Supporting

Mentioning

131

Contrasting

Order By: Relevance

“…However, we can report that the in vivo tumor-to-pancreas ratios in mouse models are more favorable for 68 Ga-NeoBOMB1 (0.6) than other GRPR antagonists such as 67 Ga-SB3 (0.2) reported by Maina et al (16) and 99m Tc-Demobesin 1 (0.2) reported by Cescato et al (numbers are based on biodistribution results 60 min after injection of the radiotracers) (13). However, lower peptide amounts were used in these studies, which could lead to less favorable results as demonstrated in the 177 Lu-NeoBOMB1 biodistribution studies.…”

Section: Discussionmentioning

confidence: 89%

“…Concerning imaging, patient studies by Maina et al (16) in which prostate cancer lesions were successfully visualized using a GRPR radioligand showed a biodistribution pattern in physiologic organs similar to what was found in mice. However, this was a pilot study in a limited number of patients, and more clinical studies are needed.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we explored the use of a novel DOTA-coupled GRPR antagonist, NeoBOMB1, derived from a previously reported GRPR antagonist, SB3 (16). The peptidic part of NeoBOMB1, however, is based on a different GRPR antagonist first described by Heimbrook et al (17) and generated by modification of the C-terminal Leu 13 -Met 14 -NH 2 and the replacement of Asn 6 by DPhe 6 of native bombesin (6)(7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

See 2 more Smart Citations

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

et al. 2016

Self Cite

View full text Add to dashboard Cite

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 68 Ga-NeoBOMB1 and 177 LuNeoBOMB1. Methods: PC-3 tumor-xenografted BALB/c nu/nu mice were injected with either approximately 13 MBq/250 pmol 68 GaNeoBOMB1 or a low (;1 MBq/200 pmol) versus 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, 120, 240, and 360 min for 68 4,24, 48, 96, and 168 h for 177 Lu-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 68 Ga-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. 177 Lu-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 0.06 mGy/MBq, respectively. Imaging studies resulted in good visualization of the tumor with both 68 Ga-NeoBOMB1 and 177 Lu-NeoBOMB1. Conclusion: Our findings indicate that 68 Ga-or 177 Lu-labeled NeoBOMB1 is a promising radiotracer with excellent tumor uptake and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…They have a stable biodistribution in healthy volunteers (15) and mean effective doses comparable to those of other radiopharmaceuticals (16,17). Data are encouraging regarding their potential for the initial diagnosis of PCa (15)(16)(17)(18)(19), for the assessment of biochemical recurrence (15,16,(18)(19)(20)(21)(22)(23), and for the theranostic approach (24). The lack of salivary or lacrimal gland uptake and the low hepatobiliary clearance give them an advantage.…”

mentioning

confidence: 94%

“…High uptake was reported in primary PCa lesions and metastases (16,18,23), but benign prostate hypertrophy resulted in false-positive findings in some cases (16). This may be avoided by the development of appropriate metrics of image interpretation.…”

mentioning

confidence: 99%

Will GRPR Compete with PSMA as a Target in Prostate Cancer?

Iagaru

2017

J Nucl Med

View full text Add to dashboard Cite

A study of radiogallium aqueous chemistry:in vitroandin vivocharacterisation of⁶⁷Ga-hydrolysed-stannous fluoride particles

Tsopelas

2016

J. Label Compd. Radiopharm

View full text Add to dashboard Cite

The objective of this study was to explore the aqueous chemistry of gallium using (67) Ga-chloride starting material, by radiolabelling hydrolysed(h)-stannous fluoride particles and then characterising the optimal formulation for radiochemical purity (RCP) and radioactive particle size distribution in vitro. The pilot reactions determined stannous fluoride was added to (67) Ga-acetate under nitrogen and then heated at 100 °C for 20 min to achieve ≥95% RCP and (67) Ga-particles were >3 µm in diameter. A high radioactive concentration of (67) Ga-h-SnF2 particles could be prepared similarly in ≥97% RCP with 74% as 3-5 µm and 26% >5 µm in diameter. The latter formulation had larger particles than (99m) Tc-h-SnF2 colloid (96% of 1-3 µm), and it resulted in a rat biodistribution of 41% in the lungs, 41% in the liver plus spleen and 18% in the carcass at 20 min after injection. The carcass activity was attributed to bone marrow and some (67) Ga-transferrin formed in blood. Isolated mixed human leucocytes were radiolabelled with (67) Ga-h-SnF2 particles in 100% efficiency, and the (67) Ga-cells did not release soluble (67) Ga(3+) at room temperature over 3 h. The (67) Ga-h-SnF2 particle formulation could find a use in labelling leucocyte cells for in vivo homing studies when delayed animal imaging is required.

show abstract

Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [68Ga]SB3 and PET/CT

Cited by 96 publications

References 34 publications

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

Will GRPR Compete with PSMA as a Target in Prostate Cancer?

A study of radiogallium aqueous chemistry:in vitroandin vivocharacterisation of⁶⁷Ga-hydrolysed-stannous fluoride particles

Contact Info

Product

Resources

About

Preclinical and first clinical experience with the gastrin-releasing peptide receptor-antagonist [68Ga]SB3 and PET/CT

Cited by 96 publications

References 34 publications

68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

Will GRPR Compete with PSMA as a Target in Prostate Cancer?

A study of radiogallium aqueous chemistry:in vitroandin vivocharacterisation of67Ga-hydrolysed-stannous fluoride particles

Contact Info

Product

Resources

About

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

⁶⁸Ga/¹⁷⁷Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

A study of radiogallium aqueous chemistry:in vitroandin vivocharacterisation of⁶⁷Ga-hydrolysed-stannous fluoride particles