Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

Rangger, Christine; Haubner, Roland

doi:10.3390/ph13020022

Cited by 37 publications

(25 citation statements)

References 245 publications

(313 reference statements)

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“…Similarly, improved detection and sensitivity could be achieved using bimodal agents [ 238 ]. Besides, the clinical success for radiolabeled somatostatin analogs both with diagnostic and therapeutic radionuclides paved the way for new promising peptide derivatives, such as bombesin, neurotensin, or CXCR4 ligands, and, in a similar way, PSMA ligands, for cancer theranostics [ 49 , 233 , 239 , 240 ].…”

Section: Future Prospectsmentioning

confidence: 99%

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Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

et al. 2020

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Identified in 1973, somatostatin (SST) is a cyclic hormone peptide with a short biological half-life. Somatostatin receptors (SSTRs) are widely expressed in the whole body, with five subtypes described. The interaction between SST and its receptors leads to the internalization of the ligand–receptor complex and triggers different cellular signaling pathways. Interestingly, the expression of SSTRs is significantly enhanced in many solid tumors, especially gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). Thus, somatostatin analogs (SSAs) have been developed to improve the stability of the endogenous ligand and so extend its half-life. Radiolabeled analogs have been developed with several radioelements such as indium-111, technetium-99 m, and recently gallium-68, fluorine-18, and copper-64, to visualize the distribution of receptor overexpression in tumors. Internal metabolic radiotherapy is also used as a therapeutic strategy (e.g., using yttrium-90, lutetium-177, and actinium-225). With some radiopharmaceuticals now used in clinical practice, somatostatin analogs developed for imaging and therapy are an example of the concept of personalized medicine with a theranostic approach. Here, we review the development of these analogs, from the well-established and authorized ones to the most recently developed radiotracers, which have better pharmacokinetic properties and demonstrate increased efficacy and safety, as well as the search for new clinical indications.

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Section: Future Prospectsmentioning

confidence: 99%

“… Comparison between [ 68 Ga]-OPS202 ( A , B ) and [ 68 Ga]-DOTATOC ( C , D ) PET/CT images of the same patient with ileal neuroendocrine tumours, showing bilobar liver metastases (from Rangger et al [ 233 ]). …”

Section: Figurementioning

confidence: 99%

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

et al. 2020

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“…The endogenous regulatory peptide is often taken as the lead sequence for development; it is iteratively truncated to identify the minimal sequence required for activity; essential AAs are determined by alanine scanning. Since regulatory peptides are prone to enzymatic degradation, modifications (e.g., D-amino acids, unnatural amino acids, backbone methylation, reduced amine bonds, cyclization) [126], can be introduced to help stabilize the peptide. The radioprosthetic group is generally appended at either the N-or C-terminus of the peptide, with some exceptions (e.g., neuropeptide Y receptor radiopharmaceuticals [127]).…”

Section: Probes Based On Bioactive Moleculesmentioning

confidence: 99%

Insight into the Development of PET Radiopharmaceuticals for Oncology

Lau

Rousseau

Kwon³

et al. 2020

Cancers

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While the development of positron emission tomography (PET) radiopharmaceuticals closely follows that of traditional drug development, there are several key considerations in the chemical and radiochemical synthesis, preclinical assessment, and clinical translation of PET radiotracers. As such, we outline the fundamentals of radiotracer design, with respect to the selection of an appropriate pharmacophore. These concepts will be reinforced by exemplary cases of PET radiotracer development, both with respect to their preclinical and clinical evaluation. We also provide a guideline for the proper selection of a radionuclide and the appropriate labeling strategy to access a tracer with optimal imaging qualities. Finally, we summarize the methodology of their evaluation in in vitro and animal models and the road to clinical translation. This review is intended to be a primer for newcomers to the field and give insight into the workflow of developing radiopharmaceuticals.

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“…We have previously applied this methodology to the assembly of a peptide conjugate comprising a modified analog of the binding sequence of the tumor-targeting peptide bombesin (BBN), namely [Nle 14 ]BBN (7)(8)(9)(10)(11)(12)(13)(14), a 99m Tc-tricarbonyl complex and the carbohydrate glucuronic acid [18]. BBN is an attractive peptide for targeting the Gastrin-releasing peptide receptor (GRPR), which is overexpressed by a variety of tumors, including prostate and breast cancer [19]. The aim of the study was to enhance the hydrophilicity of the radiolabeled peptide and therefore favoring renal over hepatobiliary excretion.…”

Section: Introductionmentioning

confidence: 99%

Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of 99mTc-Tricarbonyl-Based Radiopharmaceuticals

et al. 2020

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The organometallic technetium-99m tricarbonyl core, [99mTc][Tc(CO)3(H2O)3]+, is a versatile precursor for the development of radiotracers for single photon emission computed tomography (SPECT). A drawback of the 99mTc-tricarbonyl core is its lipophilicity, which can influence the pharmacokinetic properties of the SPECT imaging probe. Addition of polar pharmacological modifiers to 99mTc-tricarbonyl conjugates holds the promise to counteract this effect and provide tumor-targeting radiopharmaceuticals with improved hydrophilicities, e.g., resulting in a favorable fast renal excretion in vivo. We applied the “Click-to-Chelate” strategy for the assembly of a novel 99mTc-tricarbonyl labeled conjugate made of the tumor-targeting, modified bombesin binding sequence [Nle14]BBN(7–14) and the carbohydrate sorbitol as a polar modifier. The 99mTc-radiopeptide was evaluated in vitro with PC-3 cells and in Fox-1nu mice bearing PC-3 xenografts including a direct comparison with a reference conjugate lacking the sorbitol moiety. The glycated 99mTc-tricarbonyl peptide conjugate exhibited an increased hydrophilicity as well as a retained affinity toward the Gastrin releasing peptide receptor and cell internalization properties. However, there was no significant difference in vivo in terms of pharmacokinetic properties. In particular, the rate and route of excretion was unaltered in comparison to the more lipophilic reference compound. This could be attributed to the intrinsic properties of the peptide and/or its metabolites. We report a novel glycated (sorbitol-containing) alkyne substrate for the “Click-to-Chelate” methodology, which is potentially of general applicability for the development of 99mTc-tricarbonyl based radiotracers displaying an enhanced hydrophilicity.

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Radiolabelled Peptides for Positron Emission Tomography and Endoradiotherapy in Oncology

Cited by 37 publications

References 245 publications

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

Overview of Radiolabeled Somatostatin Analogs for Cancer Imaging and Therapy

Insight into the Development of PET Radiopharmaceuticals for Oncology

Sorbitol as a Polar Pharmacological Modifier to Enhance the Hydrophilicity of 99mTc-Tricarbonyl-Based Radiopharmaceuticals

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