αvβ6-integrin targeted PET/CT imaging in pancreatic cancer patients using Ga-Trivehexin.

Purpose: Ga-Trivehexin is a PET tracer targeting αvβ6-integrin, a transmembrane receptor that is frequently expressed by pancreatic cancer cells. This study aimed to determine the biokinetics, image contrast, and acquisition parameters for Ga-Trivehexin PET imaging in pancreatic cancers.

Methods: 44 patients with pancreatic cancer underwent Trivehexin PET/CT between June 2021 and November 2022 (EK-242052023).

Lead-it-EAZY! GMP-compliant production of [Pb]Pb-PSC-PEG-TOC.

Background: Recently, radiotheranostics comprising the true matched radionuclide pair Pb could serve as real dosimetric planning utility using Pb-radiolabelled pharmaceuticals before therapy with Pb-radiolabelled counterparts. Pb might act as the missing radionuclide therapy between standard β therapies (e.g.

Emerging frontiers in androgen receptor research for prostate Cancer: insights from the 2nd international androgen receptor Symposium.

Continued exploration of the androgen receptor (AR) is crucial, as it plays pivotal roles in diverse diseases such as prostate cancer (PCa), serving as a significant therapeutic focus. Therefore, the Department of Urology Dresden hosted an international meeting for scientists and clinical oncologists to discuss the newest advances in AR research. The 2nd International Androgen Receptor Symposium was held in Dresden, Saxony, Germany, from 26-27.

Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers-New Aspects and Revelations.

This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined.

Alpha-Emitting Radionuclides: Current Status and Future Perspectives.

The use of radionuclides for targeted endoradiotherapy is a rapidly growing field in oncology. In particular, the focus on the biological effects of different radiation qualities is an important factor in understanding and implementing new therapies. Together with the combined approach of imaging and therapy, therapeutic nuclear medicine has recently made great progress.

Radiosynthesis of Stable Au-Nanoparticles by Neutron Activation of αβ-Specific AuNPs for Therapy of Tumor Angiogenesis.

This paper reports on the development of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancer with high tumor angiogenesis. The AuNPs were designed with different mono- or dithiol-ligands and decorated with different amounts of Arg-Gly-Asp (RGD) peptides as a tumor-targeting vector for αβ integrin, which is overexpressed in tissues with high tumor angiogenesis. The AuNPs were evaluated for avidity in vitro and showed favorable properties with respect to tumor cell accumulation.

PET/CT imaging of head-and-neck and pancreatic cancer in humans by targeting the "Cancer Integrin" αvβ6 with Ga-68-Trivehexin.

Purpose: To develop a new probe for the αvβ6-integrin and assess its potential for PET imaging of carcinomas.

Methods: Ga-68-Trivehexin was synthesized by trimerization of the optimized αvβ6-integrin selective cyclic nonapeptide Tyr2 (sequence: c[YRGDLAYp(NMe)K]) on the TRAP chelator core, followed by automated labeling with Ga-68. The tracer was characterized by ELISA for activities towards integrin subtypes αvβ6, αvβ8, αvβ3, and α5β1, as well as by cell binding assays on H2009 (αvβ6-positive) and MDA-MB-231 (αvβ6-negative) cells.

Ac-EAZY! Towards GMP-Compliant Module Syntheses of Ac-Labeled Peptides for Clinical Application.

The application of Ac (half-life T = 9.92 d) dramatically reduces the activity used for peptide receptor radionuclide therapy by a factor of 1000 in comparison to Y, Lu or Re while maintaining the therapeutic outcome. Additionally, the range of alpha particles of Ac and its daughter nuclides in tissue is much lower (47-85 μm for alpha energies E = 5.

GMP-compliant production of [Ga]Ga-NeoB for positron emission tomography imaging of patients with gastrointestinal stromal tumor.

Background: [Ga]Ga-NeoB is a novel DOTA-coupled Gastrin Releasing Peptide Receptor (GRPR) antagonist with high affinity for GRPR and good in vivo stability. This study aimed at (1) the translation of preclinical results to the clinics and establish the preparation of [Ga]Ga-NeoB using a GMP conform kit approach and a licensed Ge/Ga generator and (2) to explore the application of [Ga]Ga-NeoB in patients with gastrointestinal stromal tumors (GIST) before and/or after interventional treatment (selective internal radiotherapy, irreversible electroporation, microwave ablation).

Results: Validation of the production and quality control of [Ga]Ga-NeoB for patient use had to be performed before starting the GMP production.

αβ-Specific Gold Nanoparticles for Fluorescence Imaging of Tumor Angiogenesis.

This paper reports on the development of tumor-specific gold nanoparticles (AuNPs) as theranostic tools intended for target accumulation and the detection of tumor angiogenesis via optical imaging (OI) before therapy is performed, being initiated via an external X-ray irradiation source. The AuNPs were decorated with a near-infrared dye, and RGD peptides as the tumor targeting vector for αβ-integrin, which is overexpressed in tissue with high tumor angiogenesis. The AuNPs were evaluated in an optical imaging setting in vitro and in vivo exhibiting favorable diagnostic properties with regards to tumor cell accumulation, biodistribution, and clearance.

Synthesis, radiolabelling and initial biological characterisation of F-labelled xanthine derivatives for PET imaging of Eph receptors.

Eph receptor tyrosine kinases, particularly EphA2 and EphB4, represent promising candidates for molecular imaging due to their essential role in cancer progression and therapy resistance. Xanthine derivatives were identified to be potent Eph receptor inhibitors with IC50 values in the low nanomolar range (1-40 nm). These compounds occupy the hydrophobic pocket of the ATP-binding site in the kinase domain.

Targeted Cu-labeled gold nanoparticles for dual imaging with positron emission tomography and optical imaging.

Gold nanoparticles (AuNPs) have been used for many years in cancer treatment mainly for brachytherapy, but in the last 15 years, the focus has shifted to the development of ultrasmall target-specific AuNPs with homogeneous size and, ultimately, tailored shapes for use in various imaging modalities such as computed tomography (CT), Raman, or photoacoustic imaging. Here, we report on the development of tumor-specific AuNPs as diagnostic tools intended for the dual detection of prostate cancer via optical imaging (OI) and positron emission tomography (PET). The AuNPs were decorated with a near-infrared dye and NODAGA chelator for complexation with radiometals.

Noncontact recognition of fluorescently labeled objects in deep tissue via a novel optical light beam arrangement.

To date, few optical imaging systems are available in clinical practice to perform noninvasive measurements transcutaneously. Instead, functional imaging is performed using ionizing radiation or intense magnetic fields in most cases. The applicability of fluorescence imaging (e.

Analyses of Synthetic N-Acyl Dopamine Derivatives Revealing Different Structural Requirements for Their Anti-inflammatory and Transient-Receptor-Potential-Channel-of-the-Vanilloid-Receptor-Subfamily-Subtype-1 (TRPV1)-Activating Properties.

We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for the activation of transient-receptor-potential channels of the vanilloid-receptor subtype 1 (TRPV1) and inhibition of inflammation. The potency of NOD in activating TRPV1 was significantly higher compared with those of variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted ( N-octanoyl tyramine), or the ester functionality consisted of a bulky fatty acid ( N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its potency, which was further increased when the carbonyl and amide groups (ΔNODR) were interchanged.

Gastrin-Releasing Peptide Receptor- and Prostate-Specific Membrane Antigen-Specific Ultrasmall Gold Nanoparticles for Characterization and Diagnosis of Prostate Carcinoma via Fluorescence Imaging.

Gold nanoparticles (AuNPs) have widely been used for 70 years in cancer treatment, but only in the last 15 years has the focus been on specific AuNPs with homogeneous size and shape for various areas in science. They constitute a perfect platform for multifunctionalization and therefore enable the enhancement of target affinity. Here we report on the development of tumor specific AuNPs as diagnostic tools intended for the detection of prostate cancer via fluorescence imaging and positron emission tomography (PET).

Correction: Synthesis, dynamic NMR characterization and XRD studies of novel ,'-substituted piperazines for bioorthogonal labeling.

[This corrects the article DOI: 10.3762/bjoc.12.

Synthesis, dynamic NMR characterization and XRD studies of novel ,'-substituted piperazines for bioorthogonal labeling.

Novel, functionalized piperazine derivatives were successfully synthesized and fully characterized by H/C/F NMR, MS, elemental analysis and lipophilicity. All piperazine compounds occur as conformers resulting from the partial amide double bond. Furthermore, a second conformational shape was observed for all nitro derivatives due to the limited change of the piperazine chair conformation.

Evaluation of two nucleophilic syntheses routes for the automated synthesis of 6-[F]fluoro-l-DOPA.

Two different strategies for the nucleophilic radiosynthesis of [F]F-DOPA were evaluated regarding their applicability for an automated routine production on an Ecker&Ziegler Modular-Lab Standard module. Initially, we evaluated a promising 5-step synthesis based on a chiral, cinchonidine-derived phase-transfer catalyst (cPTC) being described to give the product in high radiochemical yields (RCY), high specific activities (A) and high enantiomeric excesses (ee). However, the radiosynthesis of [F]F-DOPA based on this strategy showed to be highly complex, giving the intermediate products as well as the final product in insufficient yields for automatization.

Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time Transcutaneous Measurement of Renal Function.

Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPβCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPβCD was designed based on the principle of renal clearance of designed drugs.

Radiofluorinated N-Octanoyl Dopamine ([F]F-NOD) as a Tool To Study Tissue Distribution and Elimination of NOD in Vitro and in Vivo.

To mitigate pretransplantation injury in organs of potential donors, N-octanoyl dopamine (NOD) treatment might be considered as it does not affect hemodynamic parameters in braindead (BD) donors. To better assess optimal NOD concentrations for donor treatment, we report on the fast and facile radiofluorination of the NOD-derivative [F]F-NOD [F]5 for in vivo assessment of NOD's elimination kinetics by means of PET imaging. [F]5 was synthesized in reproducibly high radiochemical yields and purity (>98%) as well as high specific activities (>20 GBq/μmol).

Radiofluorination and first radiopharmacological characterization of a SWLAY peptide-based ligand targeting EphA2.

Peptides labeled with short-lived positron emitters are of considerable interest as probes for molecular imaging by positron emission tomography. Herein, the regioselective and convenient radiofluorination of a biologically relevant alkyne-modified SWLAY peptide bound on solid support with the radiolabeling building block 1-(3-azidopropyl)-4-(3-fluoropropyl)piperazine ([(18) F]AFP) is described. Peptides including this amino acid sequence are promising candidates for imaging of the erythropoietin-producing hepatoma cell line-A2 receptor (Eph), which is an interesting target for tumor imaging due to its overexpression in various tumor entities.

Recent trends in bioorthogonal click-radiolabeling reactions using fluorine-18.

The increasing application of positron emission tomography (PET) in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile bioorthogonal conjugation techniques especially for the radiolabeling of biologically active high molecular weight compounds like peptides, proteins or antibodies. Taking into consideration that the introduction of fluorine-18 (t(1/2) = 109.8 min) proceeds under harsh conditions, radiolabeling of these biologically active molecules represents an outstanding challenge and is of enormous interest.