Pre-clinical evaluation of [111In-DTPA-Pro1, Tyr4]bombesin, a new radioligand for bombesin-receptor scintigraphy

Breeman, W. A. P.; Jong, Marion de; Bernard, Bert F.; Kwekkeboom, Dik J.; Srinivasan, Ananth; Pluijm, Marcel E. van der; Hofland, Leo J.; Visser, Theo J.; Krenning, Eric P.

doi:10.1002/(sici)1097-0215(19991126)83:5<657::aid-ijc15>3.0.co;2-y

Cited by 78 publications

(68 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The first-generation radiopeptides developed for such purposes were GRPR agonists derived from C-terminal fragments of the amphibian tetradecapeptide bombesin (BBN) (7)(8)(9)(10)(11)(12) or the respective human 27mer peptide GRP (13)(14)(15). The use of resulting radioligands in humans was soon linked to undesirable effects after agonist-induced GRPR activation (16).…”

mentioning

confidence: 99%

“…Following this rationale, we have initially developed 99m Tcdemobesin 1 ( 99m Tc-DB1), a GRPR antagonist radioligand for SPECT imaging, labeled with 99m Tc and containing the [DPhe 6 , Leu-NHEt 13 ,des-Met 14 ]BBN (6)(7)(8)(9)(10)(11)(12)(13)(14) peptide fragment (17,18). To allow labeling with other clinically relevant radiometals, we then replaced the acyclic tetraamine chelator of DB1 by the universal chelator DOTA.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results

et al. 2016

Self Cite

View full text Add to dashboard Cite

We recently introduced the potent gastrin-releasing peptide receptor (GRPR) antagonist 68 Ga-SB3 ( 68 Ga-DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), showing excellent tumor localizing efficacy in animal models and in patients. By replacement of the C-terminal Leu 13 -Met 14 -NH 2 dipeptide of SB3 by Sta 13 -Leu 14 -NH 2 , the novel GRPR antagonist NeoBOMB1 was generated and labeled with different radiometals for theranostic use. We herein report on the biologic profile of resulting 67/68 111 In-, and 177 Lu-NeoBOMB1 radioligands in GRPR-expressing cells and mouse models. The first evidence of prostate cancer lesion visualization in men using 68 Ga-NeoBOMB1 and PET/CT is also presented. Methods: NeoBOMB1 was radiolabeled with 67/68 Ga, 111 In, and 177 Lu according to published protocols. The respective metalated species nat Ga-, nat In-, and nat Lu-NeoBOMB1 were also synthesized and used in competition binding experiments against [ 125 I-Tyr 4 ]BBN in GRPRpositive PC-3 cell membranes. Internalization of 67 111 In-, and 177 Lu-NeoBOMB1 radioligands was studied in PC-3 cells at 37°C, and their metabolic stability in peripheral mouse blood was determined by high-performance liquid chromatography analysis of blood samples. Biodistribution was performed by injecting a 67 111 In-, or 177 Lu-NeoBOMB1 bolus (74, 74, or 370 kBq, respectively, 100 mL, 10 pmol total peptide 6 40 nmol Tyr 4 -BBN: for in vivo GRPR blockade) in severe combined immunodeficiency mice bearing PC-3 xenografts. PET/CT images with 68 Ga-NeoBOMB1 were acquired in prostate cancer patients. Results: NeoBOMB1 and nat Ga-, nat In-, and nat LuNeoBOMB1 bound to GRPR with high affinity (half maximal inhibitory concentration, 1-2 nM). 67 111 In-, and 177 Lu-NeoBOMB1 specifically and strongly bound on the cell membrane of PC-3 cells displaying low internalization, as expected for receptor antagonists. They showed excellent metabolic stability in peripheral mouse blood (.95% intact at 5 min after injection). After injection in mice, all 3 ( 67 111 In-, and 177 Lu-NeoBOMB1) showed comparably high and GRPR-specific uptake in the PC-3 xenografts (e.g., 30.6 6 3.9, 28.6 6 6.0, and .35 percentage injected dose per gram at 4 h after injection, respectively), clearing from background predominantly via the kidneys. During a translational study in prostate cancer patients, 68 Ga-NeoBOMB1 rapidly localized in pathologic lesions, achieving high-contrast imaging. Conclusion: The GRPR antagonist radioligands 67 111 In-, and 177 Lu-NeoBOMB1, independent of the radiometal applied, have shown comparable behavior in prostate cancer models, in favor of future theranostic use in GRPR-positive cancer patients. Such translational prospects were further supported by the successful visualization of prostate cancer lesions in men using 68 Ga-NeoBOMB1 and PET/CT.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, 99m Tcand 111 In-coupled BN analogues have been developed for diagnostic SPECT imaging and 64 Cu-and 68 Ga-labelled analogues for PET imaging of GRP receptor-expressing tumours [26][27][28][29][30][31][32][33][34][35][36][37][38][39]. In addition, 90 Y-and 177 Lu-labelled analogues have been described as promising tools for targeted radiotherapy of these tumours [26,40].…”

mentioning

confidence: 99%

“…We previously developed and evaluated the radiolabelled peptide [ 111 In-DTPA-Pro 1 ,Tyr 4 ]BN, a BN analogue which internalised rapidly into GRP receptor-positive tumour cells in vitro and in vivo [37][38][39]. In addition, GRP receptorexpressing CA20948 and AR42J tumours could be visualised using gamma camera imaging in rats after injection with this radiolabelled BN analogue [37,38].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Novel 111In-labelled bombesin analogues for molecular imaging of prostate tumours

Visser

Bernard

Erion

et al. 2007

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Purpose It has been shown that some primary human tumours and their metastases, including prostate and breast tumours, overexpress gastrin-releasing peptide (GRP) (5-14)), was tested in vivo in biodistribution studies using rats bearing GRP receptor-expressing CA20948 tumours, and nude mice bearing human PC3 xenografts. Injection of 111In-labelled Cmp 3 in these animals showed high, receptor-mediated uptake in receptor-positive organs and tumours which could be visualised using planar gamma camera and microSPECT/CT imaging. Conclusion With their enhanced receptor affinity and their rapid receptor-mediated internalisation in vitro and in vivo, the new BN analogues, and especially Cmp 3, are promising candidates for use in diagnostic molecular imaging and targeted radionuclide therapy of GRP receptor-expressing cancers.

show abstract

Bombesin

Howard

Ghatei

Bloom

2002

Wiley Encyclopedia of Molecular Medicine

View full text Add to dashboard Cite

Pre-clinical evaluation of [111In-DTPA-Pro1, Tyr4]bombesin, a new radioligand for bombesin-receptor scintigraphy

Cited by 78 publications

References 22 publications

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results

Novel 111In-labelled bombesin analogues for molecular imaging of prostate tumours

Bombesin

Contact Info

Product

Resources

About