A5058629794- Radiopharmaceutical Chemistry and Applications
- Neuroendocrine Tumor Research Advances
- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Neuroblastoma Research and Treatments
- Neuropeptides and Animal Physiology
- Monoclonal and Polyclonal Antibodies Research
- Prostate Cancer Treatment and Research
- Medical Imaging Techniques and Applications
- Immunotherapy and Immune Responses
- Receptor Mechanisms and Signaling
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Atomic and Subatomic Physics Research
- Chemical Reactions and Isotopes
- Herpesvirus Infections and Treatments
- Adrenal and Paraganglionic Tumors
- Chemokine receptors and signaling
- Nutrition, Genetics, and Disease
- Prostate Cancer Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Diabetes Treatment and Management
- Nanoparticle-Based Drug Delivery
- Advanced Breast Cancer Therapies
- Click Chemistry and Applications
University Hospital of Basel
2015-2025
University of Basel
2019-2024
University Hospital of Lausanne
2023
Weatherford College
2023
University Medical Center Freiburg
2011-2016
University of Freiburg
2011-2016
University of Naples Federico II
2004-2014
Institute of Biostructure and Bioimaging
2012-2014
Centro Interuniversitario di Ricerca sui Peptidi Bioattivi
2004-2012
University of Wisconsin–Madison
2011
Somatostatin-based radiolabeled peptides have been successfully introduced into the clinic for targeted imaging and radionuclide therapy of somatostatin receptor (sst)–positive tumors, especially subtype 2 (sst2). The clinically used are exclusively agonists. Recently, we showed that antagonists may be preferable to agonists because they better pharmacokinetics, including higher tumor uptake. Factors determining performance radioantagonists only scarcely studied. Here, report on development...
Abstract Purpose: G protein–coupled receptor agonists are being used as radiolabeled vectors for in vivo localization and therapy of tumors. Recently, somatostatin-based antagonists were shown to be superior agonists. Here, we compare the new [111In/68Ga]-labeled bombesin-based antagonist RM1 with agonist [111In]-AMBA targeting gastrin-releasing peptide (GRPR). Experimental Design: IC50, Kd values, potency determined using PC-3 HEK-GRPR cells. Biodistribution imaging studies done nude mice...
Strong overexpression of glucagonlike peptide-1 (GLP-1) receptors in human insulinoma provides an attractive target for imaging. The first clinical trials demonstrated that GLP-1 receptor SPECT/CT using [Lys<sup>40</sup>(Ahx [6-aminohexanoic acid]-DOTA-<sup>111</sup>In)NH<sub>2</sub>]-exendin-4 can localize hardly detectable insulinomas. However, [Lys<sup>40</sup>(Ahx-DOTA-<sup>111</sup>In)NH<sub>2</sub>]-exendin-4 imaging has drawbacks related to the use <sup>111</sup>In it is costly and...
Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for cancer imaging and targeted radiotherapy.Methods: Biodistribution, dosimetry tumor uptake of GRPr antagonist 64 Cu-CB-TE2A-AR06 [( Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG 4 -D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH 2 ] were studied by PET/CT in four patients with newly diagnosed (T1c-T2b,...
Radiolabeled somatostatin receptor (SSTR) antagonists have shown in vivo higher uptake SSTR-expressing tumors than agonists. In this preclinical study, the SSTR2 antagonist OPS201 (DOTA-JR11; DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH<sub>2</sub>]) labeled with <sup>177</sup>Lu, <sup>90</sup>Y, and <sup>111</sup>In was compared agonist <sup>177</sup>Lu-DOTATATE. <b>Methods:</b> Biodistribution, pharmacokinetics, SPECT/CT, dosimetry studies were performed to assess...
Fibroblast activation protein-α (FAP)-targeting radioligands have recently demonstrated high diagnostic potential. However, their therapeutic value is impaired by the short tumor residence time. Several strategies been tested to overcome this limitation, but a head-to-head comparison has never done. With aim identify strengths and limitations of suggested strategies, we compared monomer FAPI-46 versus (a) its dimer (FAPI-46-F1D), (b) two albumin binders conjugates (FAPI-46-Ibu (ibuprofen)...
Bombesin receptors are overexpressed on a variety of human tumors. In particular, the gastrin-releasing peptide receptor (GRPr) has been identified prostate and breast cancers gastrointestinal stromal The current study aims at developing clinically translatable bombesin antagonist–based radioligands for SPECT PET GRPr-positive <b>Methods:</b> A potent antagonist (PEG<sub>4</sub>-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH<sub>2</sub> [AR]) was synthesized; conjugated to chelators DOTA,...
The gastrin-releasing peptide receptor (GRPr) is overexpressed in prostate cancer and an attractive target for radionuclide therapy. In addition, inhibition of the protein kinase mammalian rapamycin (mTOR) has been shown to sensitize various cells effects radiotherapy. <b>Methods:</b> To determine effect treatment with radiotherapy a novel <sup>177</sup>Lu-labeled GRPr antagonist (<sup>177</sup>Lu-RM2, BAY 1017858) alone combination, vitro vivo studies were performed using human PC-3 cell...
Radiolabeled hybrid ligands with defined distances between an agonist and antagonist for the gastrin-releasing peptide receptor were found to have excellent tumor-targeting properties. Oligoprolines served as rigid scaffolds that allowed tailoring of 10, 20, 30 Å recognition elements. In vitro in vivo studies revealed ligand a distance 20 elements exhibits highest yet observed tumor cell uptake retention time prostate cancer cells.
Patients with metastatic medullary thyroid cancer (MTC) have limited systemic treatment options. The use of radiolabeled gastrin analogs targeting the cholecystokinin-2 receptor (CCK2R) is an attractive approach. However, their therapeutic efficacy presumably decreased by enzymatic degradation in vivo. We aimed to investigate whether chemically stabilized analog <sup>177</sup>Lu-DOTA-PP-F11N (<sup>177</sup>Lu-DOTA-(dGlu)<sub>6</sub>-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH<sub>2</sub>) performs better...
Gastrin-releasing peptide receptors (GRPrs) are overexpressed on a variety of human cancers, providing the opportunity for receptor targeting via radiolabeled bombesin-based peptides. As part our ongoing investigations into development improved GRPr antagonists, this study aimed at verifying whether and how N-terminal modulations improve affinity pharmacokinetics antagonists. <b>Methods:</b> The potent antagonist MJ9, Pip-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH<sub>2</sub> (Pip,...
From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, (111)In-CP04 ((111)In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as diagnostic radiopharmaceutical towards first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation multicentre application has been developed. We herein report on biosafety, vivo stability, biodistribution dosimetry aspects animal models, essential the regulatory...
The demand for PET tracers that target prostate-specific membrane antigen (PSMA) continues to increase. Meeting this with approved <sup>68</sup>Ga- and <sup>18</sup>F-labeled PSMA is challenging outside of major urban centers. This because the short physical half-life these radionuclides makes it necessary produce them near their sites usage. To overcome challenge, we propose cyclotron-produced <sup>61</sup>Cu labeling tracers. can be produced on a large scale, its 3.33-h allows shipping...
The development of metabolically stable radiolabeled gastrin analogues with suitable pharmacokinetics is a topic recent research activity. These imaging vectors are interest because the gastrin/CCK2 receptor highly overexpressed in different tumors such as medullary thyroid cancer, neuroendocrine tumors, and SCLC. drawback current targeting agents either their metabolic instability or high kidney uptake. We present synthesis vitro vivo evaluation 11 (111)In-labeled DOTA-conjugated peptides...
The C‐X‐C chemokine receptor 4 (CXCR4) is highly upregulated in most cancers, making it an ideal target for delivering radiation therapy to tumors. We previously demonstrated the feasibility of targeting CXCR4 vivo using a radiolabeled derivative EPI‐X4, endogenous antagonist, named DOTA‐K‐JM#173. However, this showed undesirable accumulation kidneys, which would limit its clinical use. In study, we identified that removing positive charge from peptide sequence significantly reduced renal...
The present work describes new supramolecular aggregates obtained by co-assembling two different amphiphilic molecules, one containing the bioactive bombesin peptide (BN), or a scramble sequence, and other, DOTA chelating agent, (C18)2DOTA, capable of forming stable complexes with radioactive 111In(III) isotope. in monomer is spaced lipophilic moiety through ethoxylic spacers length: shorter spacer five units dioxoethylene moieties (C18)2L5-peptide, longer consisting Peg3000 residue...