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03-02-2025 | Original Article

[113mIn]In-AMBA: A Novel Diagnostic Agent for SPECT Imaging of GRPR-Expressing Tumors

Authors: Mohammad Moazami-Ashtiani, Saeed Rajabifar, Samaneh Zolghadri, Hassan Yousefnia

Published in: Nuclear Medicine and Molecular Imaging

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Abstract

Purpose

Gastrin-releasing peptide receptor (GRPR), a member of the bombesin G-protein-coupled receptor family, is introduced as the promising target for the diagnosis and therapy of various tumors. This study aimed to develop a novel diagnostic agent of [113mIn]In-AMBA for single photon emission computed tomography (SPECT) imaging of GRPR expressing tumors.

Methods

113mIn was provided from an in-house made 113Sn/113mIn generator in the chloride form. [113mIn]In-AMBA was prepared in the optimal conditions and the stability was checked in PBS buffer and human serum, Then the binding affinity and internalization of the radiolabeled compound were investigated in PC3 cell lines at 120 min. the biodistribution of the radiolabeled peptide was studied in normal rats.

Results

[113mIn]In-AMBA was prepared with radiochemical purity (RCP) > 98% under the optimal labeling conditions. The compound indicated significant stability in PBS buffer and human serum (> 95% at 180 min post preparation). High binding affinity (51% at 60 min) and internalization (64% at 120 min) of the radiolabeled compound towards PC3 cell lines were also observed. The major accumulation of the compound was seen in kidneys, and other GRPR-expressing tissues.

Conclusion

The biodistribution of the labeled compound in normal rats indicated rapid elimination of the complex from the blood, and considerable accumulation in the GRPR-expressing organ of pancreas, in complete agreement with similar labeled compounds. [113mIn]In-AMBA can be a suitable candidate for SPECT imaging of GRPR-expressed tumors.
Literature
1.
go back to reference Clancy E. ACS Report Shows Prostate Cancer on the Rise, Cervical Cancer on the Decline. Renal & Urology News. 2023; 23: NA. Clancy E. ACS Report Shows Prostate Cancer on the Rise, Cervical Cancer on the Decline. Renal & Urology News. 2023; 23: NA.
2.
go back to reference Lindsley CW, Müller CE, Bongarzone S. Diagnostic and therapeutic radiopharmaceuticals. ACS Pharmacol Transl Sci. 2022;19:835–7.CrossRef Lindsley CW, Müller CE, Bongarzone S. Diagnostic and therapeutic radiopharmaceuticals. ACS Pharmacol Transl Sci. 2022;19:835–7.CrossRef
4.
go back to reference Badipa F, Alirezapour B, Yousefnia H. An overview of radiolabeled RGD peptides for Theranostic Applications. Curr Radiopharm. 2023;16:107–22.CrossRefPubMed Badipa F, Alirezapour B, Yousefnia H. An overview of radiolabeled RGD peptides for Theranostic Applications. Curr Radiopharm. 2023;16:107–22.CrossRefPubMed
6.
go back to reference Morgat C, MacGrogan G, Brouste V, Vélasco V, Sevenet N, Bonnefoi H, et al. Expression of gastrin-releasing peptide receptor in breast cancer and its association with pathologic, biologic, and clinical parameters: a study of 1,432 primary tumors. J Nucl Med. 2017;58:1401–7.CrossRefPubMed Morgat C, MacGrogan G, Brouste V, Vélasco V, Sevenet N, Bonnefoi H, et al. Expression of gastrin-releasing peptide receptor in breast cancer and its association with pathologic, biologic, and clinical parameters: a study of 1,432 primary tumors. J Nucl Med. 2017;58:1401–7.CrossRefPubMed
7.
go back to reference Moreno P, Ramos-Álvarez I, Moody TW, Jensen RT. Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment. Expert Opin Ther Targets. 2016;20:1055–73.CrossRefPubMedPubMedCentral Moreno P, Ramos-Álvarez I, Moody TW, Jensen RT. Bombesin related peptides/receptors and their promising therapeutic roles in cancer imaging, targeting and treatment. Expert Opin Ther Targets. 2016;20:1055–73.CrossRefPubMedPubMedCentral
8.
go back to reference de Aguiar Ferreira C, Fuscaldi LL, Townsend DM, Rubello D, de Barros AL. Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed Pharmacother. 2017;87:58–72.CrossRef de Aguiar Ferreira C, Fuscaldi LL, Townsend DM, Rubello D, de Barros AL. Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed Pharmacother. 2017;87:58–72.CrossRef
9.
go back to reference Li X, Cai H, Wu X, Li L, Wu H, Tian R. New frontiers in molecular imaging using peptide-based radiopharmaceuticals for prostate cancer. Front Chem. 2020;8:583309.CrossRefPubMedPubMedCentral Li X, Cai H, Wu X, Li L, Wu H, Tian R. New frontiers in molecular imaging using peptide-based radiopharmaceuticals for prostate cancer. Front Chem. 2020;8:583309.CrossRefPubMedPubMedCentral
10.
go back to reference Lantry LE, Cappelletti E, Maddalena ME, Fox JS, Feng W, Chen J, et al. 177Lu-AMBA: synthesis and characterization of a selective 177Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. J Nucl Med. 2006;47:1144–52.PubMed Lantry LE, Cappelletti E, Maddalena ME, Fox JS, Feng W, Chen J, et al. 177Lu-AMBA: synthesis and characterization of a selective 177Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. J Nucl Med. 2006;47:1144–52.PubMed
11.
go back to reference Lantry LE, Thomas R, Waser B, Maddalena M, Fox JS, Arunachalam T, et al. Preclinical evaluation of Lu-177-AMBA, a DOTA conjugate that targets GRP and NMB receptor expressing tumors: internalization, in vivo biodistribution, single dose radiotherapy in PC-3 tumor-bearing nude mice and in vitro autoradiography in animal and human tissues. Eur J Nucl Med Mol Imaging. 2004;31:S389–90. Lantry LE, Thomas R, Waser B, Maddalena M, Fox JS, Arunachalam T, et al. Preclinical evaluation of Lu-177-AMBA, a DOTA conjugate that targets GRP and NMB receptor expressing tumors: internalization, in vivo biodistribution, single dose radiotherapy in PC-3 tumor-bearing nude mice and in vitro autoradiography in animal and human tissues. Eur J Nucl Med Mol Imaging. 2004;31:S389–90.
12.
go back to reference Baum R, Prasad V, Mutloka N, Frischknecht M, Maecke H, Reubi J. Molecular imaging of bombesin receptors in various tumors by Ga-68 AMBA PET/CT: first results. J Nucl Med. 2007;48(supplement 2):79P. Baum R, Prasad V, Mutloka N, Frischknecht M, Maecke H, Reubi J. Molecular imaging of bombesin receptors in various tumors by Ga-68 AMBA PET/CT: first results. J Nucl Med. 2007;48(supplement 2):79P.
13.
go back to reference Zhang-Yin J, Provost C, Cancel-Tassin G, Rusu T, Penent M, Radulescu C, et al. A comparative study of peptide-based imaging agents [68Ga] Ga-PSMA-11, [68Ga]Ga-AMBA, [68Ga]Ga-NODAGA-RGD and [68Ga]Ga-DOTA-NT-20.3 in preclinical prostate tumour models. Nucl Med Biol. 2020;84:88–95.CrossRefPubMed Zhang-Yin J, Provost C, Cancel-Tassin G, Rusu T, Penent M, Radulescu C, et al. A comparative study of peptide-based imaging agents [68Ga] Ga-PSMA-11, [68Ga]Ga-AMBA, [68Ga]Ga-NODAGA-RGD and [68Ga]Ga-DOTA-NT-20.3 in preclinical prostate tumour models. Nucl Med Biol. 2020;84:88–95.CrossRefPubMed
14.
go back to reference Ho CL, Liu IH, Wu YH, Chen LC, Chen CL, Lee WC et al. Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in human prostate Tumor‐Bearing mice. BioMed Res Int 2011;101497. Ho CL, Liu IH, Wu YH, Chen LC, Chen CL, Lee WC et al. Molecular Imaging, Pharmacokinetics, and Dosimetry of 111In-AMBA in human prostate Tumor‐Bearing mice. BioMed Res Int 2011;101497.
15.
go back to reference Fox J, Maddalena ME, Wedeking P, Chen J, Wang N, Linder K et al. 2007. Comparative biodistributions of 111In, 67Ga and 177Lu-AMBA in PC-3 tumor bearing mice. J Nucl Med. 79P. Fox J, Maddalena ME, Wedeking P, Chen J, Wang N, Linder K et al. 2007. Comparative biodistributions of 111In, 67Ga and 177Lu-AMBA in PC-3 tumor bearing mice. J Nucl Med. 79P.
16.
go back to reference Chen J, Feng W, Arunachalam T, Metcalfe E, Nunn A, Linder K. Preparation and in vitro binding of 67Ga-AMBA, comparison to 177Lu-AMBA. Nucl Med; 2007; 48 (supplement 2) 306P. Chen J, Feng W, Arunachalam T, Metcalfe E, Nunn A, Linder K. Preparation and in vitro binding of 67Ga-AMBA, comparison to 177Lu-AMBA. Nucl Med; 2007; 48 (supplement 2) 306P.
17.
go back to reference Bolorinovin F, Mirzaei M, Faghihi R, Joharidaha F, Sina S, Hadad K, et al. Design and construction of a 113Sn/113mIn generator using irradiation of natural indium in a cyclotron accelerator. JONSAT. 2024;45:99–106. Bolorinovin F, Mirzaei M, Faghihi R, Joharidaha F, Sina S, Hadad K, et al. Design and construction of a 113Sn/113mIn generator using irradiation of natural indium in a cyclotron accelerator. JONSAT. 2024;45:99–106.
18.
go back to reference Akbari L, Sina S, Zolghadri S, Moghaddasi A, Hadad K, Yousefnia H. [113mIn]In-PSMA: high potential agent for SPECT imaging of prostate cancer. Radiochim Acta. 2024;112:883–94.CrossRef Akbari L, Sina S, Zolghadri S, Moghaddasi A, Hadad K, Yousefnia H. [113mIn]In-PSMA: high potential agent for SPECT imaging of prostate cancer. Radiochim Acta. 2024;112:883–94.CrossRef
20.
go back to reference Stern HS, Zolle I, McAfee JG. Preparation of technetium (Tc99m)-labeled serum albumin (human). Appl Radiat Isot. 1965;16:283–8.CrossRef Stern HS, Zolle I, McAfee JG. Preparation of technetium (Tc99m)-labeled serum albumin (human). Appl Radiat Isot. 1965;16:283–8.CrossRef
21.
go back to reference Rookeman VA, Sun PC, Bruno FP, Dunavant BG. Internal distribution and absorbed dose calculations for radioactive indium liver and lung scanning agents. AJR Am J Roentgenol. 1970;109:735–41. Rookeman VA, Sun PC, Bruno FP, Dunavant BG. Internal distribution and absorbed dose calculations for radioactive indium liver and lung scanning agents. AJR Am J Roentgenol. 1970;109:735–41.
22.
go back to reference Potchen EJ, Adatepe M, Welch M, Archer E, Studer R. Indium in 113m for visualizing Body organs: a broad spectrum scanning Agent. JAMA. 1968;205:208–12.CrossRefPubMed Potchen EJ, Adatepe M, Welch M, Archer E, Studer R. Indium in 113m for visualizing Body organs: a broad spectrum scanning Agent. JAMA. 1968;205:208–12.CrossRefPubMed
23.
go back to reference O’Mara RE, Subramanian G, McAfee JG, Burger CL. Comparison of 113mIn and other short-lived agents for cerebral scanning. J Nucl Med. 1969;10:18–27.PubMed O’Mara RE, Subramanian G, McAfee JG, Burger CL. Comparison of 113mIn and other short-lived agents for cerebral scanning. J Nucl Med. 1969;10:18–27.PubMed
24.
go back to reference Bolourinovin F, Mirzaei M, Faghihi R, Joharidaha F, Sina S, Hadad K, et al. Preparation, Quality control, Biodistribution of [113mIn]In-DOTATATE. JONSAT. 2024;45:29–35. Bolourinovin F, Mirzaei M, Faghihi R, Joharidaha F, Sina S, Hadad K, et al. Preparation, Quality control, Biodistribution of [113mIn]In-DOTATATE. JONSAT. 2024;45:29–35.
25.
go back to reference Chen J, Linder KE, Cagnolini A, Metcalfe E, Raju N, Tweedle MF, et al. Synthesis, stabilization and formulation of [177Lu] Lu-AMBA, a systemic radiotherapeutic agent for gastrin releasing peptide receptor positive tumors. Appl Radiat Isot. 2008;66:497–505.CrossRefPubMed Chen J, Linder KE, Cagnolini A, Metcalfe E, Raju N, Tweedle MF, et al. Synthesis, stabilization and formulation of [177Lu] Lu-AMBA, a systemic radiotherapeutic agent for gastrin releasing peptide receptor positive tumors. Appl Radiat Isot. 2008;66:497–505.CrossRefPubMed
26.
go back to reference Pandey U, Mukherjee A, Jindal A, Gamre N, Korde A, Ram R, et al. Preparation and evaluation of a single vial AMBA kit for 68 Ga labeling with potential for imaging of GRP receptor-positive cancers. J Radioanal Nucl Chem. 2016;307:1115–24.CrossRef Pandey U, Mukherjee A, Jindal A, Gamre N, Korde A, Ram R, et al. Preparation and evaluation of a single vial AMBA kit for 68 Ga labeling with potential for imaging of GRP receptor-positive cancers. J Radioanal Nucl Chem. 2016;307:1115–24.CrossRef
Metadata
Title
[113mIn]In-AMBA: A Novel Diagnostic Agent for SPECT Imaging of GRPR-Expressing Tumors
Authors
Mohammad Moazami-Ashtiani
Saeed Rajabifar
Samaneh Zolghadri
Hassan Yousefnia
Publication date
03-02-2025
Publisher
Springer Nature Singapore
Published in
Nuclear Medicine and Molecular Imaging
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-025-00906-4