68Ga-labelled-exendin-4: New GLP1R targeting agents for imaging pancreatic β-cell and insulinoma

Li, Linlin; Zhao, Ruiyue; Hong, Haiyan; Li, Guangwen; Zhang, Yan; Luo, Yang; Zha, Zhihao; Zhu, Jin-Xia; Qiao, Jie; Zhu, Lin; Kung, Hank F.

doi:10.1016/j.nucmedbio.2021.10.001

Cited by 7 publications

(11 citation statements)

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“…It was shown that the DOTAGA chelator gave the best results in vitro and in vivo , and that the THP chelator, a priori the best suited chelator among the ones investigated for kit formulation thanks to its radiolabeling characteristics, led to poor tumor uptake. Several chelators have been conjugated with exendin-4 (DOTA, NODAGA, DFO, and HBED-CC), and some of them are suitable for cold kit preparation ( 130 , 204 , 205 ).…”

Section: Cold Kitsmentioning

confidence: 99%

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

Lepareur

2022

Front. Med.

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Over the last couple of decades, gallium-68 (68Ga) has gained a formidable interest for PET molecular imaging of various conditions, from cancer to infection, through cardiac pathologies or neuropathies. It has gained routine use, with successful radiopharmaceuticals such as somatostatin analogs ([68Ga]Ga-DOTATOC and [68Ga]GaDOTATATE) for neuroendocrine tumors, and PSMA ligands for prostate cancer. It represents a major clinical impact, particularly in the context of theranostics, coupled with their 177Lu-labeled counterparts. Beside those, a bunch of new 68Ga-labeled molecules are in the preclinical and clinical pipelines, with some of them showing great promise for patient care. Increasing clinical demand and regulatory issues have led to the development of automated procedures for the production of 68Ga radiopharmaceuticals. However, the widespread use of these radiopharmaceuticals may rely on simple and efficient radiolabeling methods, undemanding in terms of equipment and infrastructure. To make them technically and economically accessible to the medical community and its patients, it appears mandatory to develop a procedure similar to the well-established kit-based 99mTc chemistry. Already available commercial kits for the production of 68Ga radiopharmaceuticals have demonstrated the feasibility of using such an approach, thus paving the way for more kit-based 68Ga radiopharmaceuticals to be developed. This article discusses the development of 68Ga cold kit radiopharmacy, including technical issues, and regulatory aspects.

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Section: Cold Kitsmentioning

confidence: 99%

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

Lepareur

2022

Front. Med.

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“…Insulinoma is a type of neuroendocrine tumor, and derived from that, the growth of β cells in the pancreas is out of control. Insulinoma is a primary cause of endogenous hypoglycemia in adult patients 4,5 . Patients with insulinoma show an abnormally high insulin concentrations along with hypoglycemia.…”

Section: Introductionmentioning

confidence: 99%

“…There are several challenges in searching for suitable imaging agents that can selectively bind to β cells and reflect BCM. In the pancreas, β cells represent only about 1%−2% of the total pancreatic cells mass 4 . This low target density requires a tracer to have high specificity to bind to the target receptor.…”

Section: Introductionmentioning

confidence: 99%

“…Insulinoma is a primary cause of endogenous hypoglycemia in adult patients. 4,5 Patients with insulinoma show an abnormally high insulin concentrations along with hypoglycemia. Conventional imaging techniques such as magnetic resonance imaging (MRI), computed tomography (CT), and endoscopic ultrasonography (EUS) have limited sensitivity and resolution in locating insulinoma because the small size of tumor is less than 1 cm.…”

mentioning

confidence: 99%

“…In the pancreas, β cells represent only about 1%À2% of the total pancreatic cells mass. 4 This low target density requires a tracer to have high specificity to bind to the target receptor. Meanwhile, the target receptor could only be selectively present in the β cells, rather than other types of pancreatic cells.…”

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confidence: 99%

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In vivo and in vitro binding of [¹²⁵I]I‐R‐(+)‐TISCH: A dopamine D₁ receptor ligand for studying pancreatic β‐cell mass

Zhang

Sun

et al. 2022

Labelled Comp Radiopharmac

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Comparison of the Tissue Distribution of a Long-Circulating Glucagon-like Peptide-1 Agonist Determined by Positron Emission Tomography and Quantitative Whole-Body Autoradiography

Fernandes

Wilbs

Raavé

et al. 2022

ACS Pharmacol. Transl. Sci.

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Positron emission tomography (PET) is a molecular imaging modality that enables non-invasive visualization of tracer distribution and pharmacology. Recently, peptides with long half-lives allowed once-a-week dosing of glucagon-like peptide-1 receptor (GLP-1R) agonists with therapeutic applications in diabetes and obesity. PET imaging for such long-lived peptides is hindered by the typically used short-lived radionuclides. Zirconium-89 ( 89 Zr) emerged as a promising PET radionuclide with a sufficiently long half-life to be applied for biodistribution studies of long-circulating biomolecules. A comparison between the biodistribution profiles obtained via 89 Zr-PET and the current standard, quantitative whole-body autoradiography (QWBA), will be valuable for the development of novel peptide drugs. We determined the PET biodistribution of a 89 Zr-labeled acylated peptide agonist of GLP-1R and compared it to the profile obtained by QWBA using analogous tritiated tracers for up to 1 week after administration. The plasma metabolic profile was obtained and identification was done for the tritiated tracers. We found that, at early time points, the biodistribution profiles agreed between PET and QWBA. At the latertime points, the 89 Zr tracer remained primarily trapped in the kidneys. The introduction of desferrioxamine (DFO) chelator reduced the peptide stability, and UPLC-MS analysis identified a circulating metabolite arising from DFO hydrolysis. Kidney accumulation of radiolabeled peptides and DFO metabolic instability may compromise biodistribution studies using 89 Zr-PET to support the development of new biopharmaceuticals. PET and QWBA biodistribution data correlated well during the absorption phase, but new and more stable 89 Zr chelators are needed for a more accurate description of the elimination phase.

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68Ga-labelled-exendin-4: New GLP1R targeting agents for imaging pancreatic β-cell and insulinoma

Cited by 7 publications

References 50 publications

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

In vivo and in vitro binding of [¹²⁵I]I‐R‐(+)‐TISCH: A dopamine D₁ receptor ligand for studying pancreatic β‐cell mass

Comparison of the Tissue Distribution of a Long-Circulating Glucagon-like Peptide-1 Agonist Determined by Positron Emission Tomography and Quantitative Whole-Body Autoradiography

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68Ga-labelled-exendin-4: New GLP1R targeting agents for imaging pancreatic β-cell and insulinoma

Cited by 7 publications

References 50 publications

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

Cold Kit Labeling: The Future of 68Ga Radiopharmaceuticals?

In vivo and in vitro binding of [125I]I‐R‐(+)‐TISCH: A dopamine D1 receptor ligand for studying pancreatic β‐cell mass

Comparison of the Tissue Distribution of a Long-Circulating Glucagon-like Peptide-1 Agonist Determined by Positron Emission Tomography and Quantitative Whole-Body Autoradiography

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In vivo and in vitro binding of [¹²⁵I]I‐R‐(+)‐TISCH: A dopamine D₁ receptor ligand for studying pancreatic β‐cell mass