Erratum to: 64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats

Mikkola, Kirsi; Yim, Cheng‐Bin; Fagerholm, Veronica; Ishizu, Tamiko; Elomaa, V.‐V.; Rajander, Johan; Jurttila, Jori; Saanijoki, Tiina; Tolvanen, Tuula; Tirri, Marko; Gourni, Eleni; Béhé, Martin; Gotthardt, Martin; Reubi, Jean Claude; Mäcke, Helmut R.; Roivainen, Anne; Solin, Olof; Nuutila, Pirjo

doi:10.1007/s11307-013-0700-5

Cited by 44 publications

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“…The purity was analyzed using analytic reversed-phase high-performance liquid chromatography on an analytic 120-5 C18 Nucleosil column, with a linear gradient of 15%-90% solvent B in 25 min at a flow rate of 1 mL/min (solvent A, 0.1% trifluoroacetic acid/H2O; solvent B, 0.1% trifluoroacetic acid/acetonitrile). The nat Ga complexation was performed as recently published (27), and 125 I-BH-Ex(9-39)NH 2 (specific activity, 81.4 MBq/nmol) was purchased from Perkin-Elmer. Ex(9-39)NH 2 was purchased from Bachem.…”

Section: Peptides and Radiochemistrymentioning

confidence: 99%

“…Lys 27 was identified as the only position to result in an 125 I-labeled agent that showed the same performance in human tissue binding assays as the potent agonist 125 I-GLP-1(7-36)NH 2 (22). We therefore hypothesized that modification at Lys 27 with chelates may lead to more potent radiometal-labeled GLP-1 receptor antagonists than the modification at Lys 40 .…”

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confidence: 99%

“…Radioiodine belongs to the no-residualizing labels and will not be retained in the kidney after reabsorption and degradation in the proximal tubular cells (23)(24)(25). Therefore, we compared the performance of Ex(9-39)NH 2 antagonists, conjugated to chelates at positions Lys 27 …”

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confidence: 99%

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Approaches to Improve the Pharmacokinetics of Radiolabeled Glucagon-Like Peptide-1 Receptor Ligands Using Antagonistic Tracers

Rylova

Waser

Pozzo³

et al. 2016

J Nucl Med

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The glucagon-like peptide-1 (GLP-1) receptors are important biomarkers for imaging pancreatic β-cell mass and detection of benign insulinomas. Using GLP-1 receptor antagonists, we aimed to eliminate the insulin-related side effects reported for all GLP-1 receptor agonists. Additionally, using a nonresidualizing tracer, 125 I-BoltonHunter-Exendin(9-39)NH 2 ( 125 I-BH-Ex(9-39)NH 2 ), we aimed to reduce the high kidney uptake, enabling a better detection of insulinomas in the tail and head of the pancreas. Methods: The affinity and biodistribution of Ex (9- ) uptake in Ins-1E tumor, 12.5 ± 2.2 %IA/g in the pancreas, and 235.8 ± 17.0 %IA/g in the kidney, with tumor-to-blood and tumor-to-kidney ratios of 100.52 and 0.17, respectively. Biodistribution of [Lys 40 (NODAGA-68 Ga)NH 2 ]Ex(9-39) showed only 2.2 ± 0.2 %IA/g uptake in Ins-1E tumor, 1.0 ± 0.1 %IA/g in the pancreas, and 78.4 ± 8.5 %IA/g in the kidney at 1 h after injection, with tumor-to-blood and tumor-to-kidney ratios of 7.33 and 0.03, respectively. In contrast, 125 I-BH-Ex(9-39)NH 2 showed tumor uptake (42.5 ± 8.1 %IA/g) comparable to the agonist and 28.8 ± 5.1 %IA/g in the pancreas at 1 h after injection. As we hypothesized, the kidney uptake of 125 I-BH-Ex(9-39)NH 2 was low, only 12.1 ± 1.4 %IA/g at 1 h after injection. The tumor-to-kidney ratio of 125 I-BH-Ex(9-39)NH 2 was improved 20-fold. Conclusion: Our results suggest that iodinated Ex(9-39)NH 2 may be a promising tracer for imaging GLP-1 receptor expression in vivo. Because of the 20-fold improved tumorto-kidney ratio 125 I-BH-Ex(9-39)NH 2 may offer higher sensitivity in the detection of insulinomas and imaging of β-cell mass in diabetic patients. Further studies with 124 I-BH-Ex(9-39)NH 2 are warranted.Key Words: GLP-1 receptor; insulinoma; β-cell mass; antagonist The glucagon-like peptide (GLP-1) receptors are important targets because they are overexpressed on more than 90% of benign insulinomas, some malignant insulinomas, most gastrinomas, and most phaeochromocytomas (1). Physiologically they are also expressed in the endocrine pancreas. Preoperative imaging of insulinomas is critical, because it helps to precisely localize these often very small lesions in the pancreas. Therefore, imaging probes for optical (2), bimodal (3), SPECT (4-7), and PET (8-13) imaging as well as MRI (14) were developed to localize GLP-1 receptors preoperatively and in addition to determine b-cell mass in diabetic animal models and potentially in patients. In particular, SPECT (4,5,7) and PET (8,13,15) agents were successfully translated into the clinic, and several promising clinical studies were reported. Still, there are a few shortcomings with the available tracers. The tracers accumulate highly in the kidneys when residualizing radiometals are used for labeling, possibly leading to not only unnecessary high radiation doses but also problems in localizing tumors in the tail and head of the pancreas (5,8,13). The usually low specific activity of the imaging tracers, exclusively agonists, and the concomitant relative...

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Section: Peptides and Radiochemistrymentioning

confidence: 99%

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confidence: 99%

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Approaches to Improve the Pharmacokinetics of Radiolabeled Glucagon-Like Peptide-1 Receptor Ligands Using Antagonistic Tracers

Rylova

Waser

Pozzo³

et al. 2016

J Nucl Med

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“…However, as presented in Figure 3, this uptake was the lowest for the oxidized form of Exendin-4, suggesting that the receptor affinity is enhanced by methionine oxidation. In our study 68 Ga-NODAGA-Nle 14 -Exendin-4 served as an internal standard for comparison of specific uptake to the GLP-1R expressing organs since it was well characterized previously both in terms of receptor binding affinity and biodistribution and tumor visualization in animals [22]. High receptor affinity was reported for [ nat Ga-NODAGA--Nle 14 -Exendin-4], the IC 50 value was 2.17 ± 0.42 nM while for native GLP-1 it was 1.0 ± 0.2 nM.…”

Section: Discussionmentioning

confidence: 99%

“…Although the development of several radiolabeled Exendin-4 analogs has been reported, the GLP-1 receptor affinities of these analogs, assessed in various cell lines do not differ significantly [8,12,[19][20][21][22]. However, so far, there is no published data on the GLP-1 receptor affinity of the oxidized form of Exendin-4.…”

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Oxidation of methionine — is it limiting the diagnostic properties of 99mTc-labeled Exendin-4, a Glucagon-Like Peptide-1 receptor agonist?

et al. 2016

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Exendin‐4 analogs in insulinoma theranostics

Jansen

Lith

Boss

et al. 2019

Labelled Comp Radiopharmac

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Insulinomas are neuroendocrine tumors arising from the pancreatic beta cells. Currently, surgical resection is the therapy of choice, and therefore, preoperative localization of insulinomas is essential. Nearly all insulinomas show overexpression of the glucagon‐like peptide‐1 receptor (GLP‐1R), and therefore, radiolabeled GLP‐1 peptide analog exendin‐4 can be used for diagnosis and preoperative localization with nuclear imaging. Here, we present an overview of the development and clinical implementation of exendin‐4–based tracers for single‐photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging of insulinomas, and we address the potential use of this molecule for optical imaging. At last, we discuss the possibilities and pitfalls of the use of exendin‐4–based tracers for therapeutic applications such as peptide receptor radionuclide therapy (PRRT) or targeted photodynamic therapy (tPDT), giving a future outlook on the use of exendin‐4 in insulinoma theranostics.

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Erratum to: 64Cu- and 68Ga-Labelled [Nle14,Lys40(Ahx-NODAGA)NH2]-Exendin-4 for Pancreatic Beta Cell Imaging in Rats

Cited by 44 publications

References 0 publications

Approaches to Improve the Pharmacokinetics of Radiolabeled Glucagon-Like Peptide-1 Receptor Ligands Using Antagonistic Tracers

Approaches to Improve the Pharmacokinetics of Radiolabeled Glucagon-Like Peptide-1 Receptor Ligands Using Antagonistic Tracers

Oxidation of methionine — is it limiting the diagnostic properties of 99mTc-labeled Exendin-4, a Glucagon-Like Peptide-1 receptor agonist?

Exendin‐4 analogs in insulinoma theranostics

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