Toward Optimized Zr-Immuno-PET: Side-by-Side Comparison of [Zr]Zr-DFO-, [Zr]Zr-3,4,3-(LI-1,2-HOPO)- and [Zr]Zr-DFO*-Cetuximab for Tumor Imaging: Which Chelator Is the Most Suitable?

89Zr represents a highly favorable positron emitter for application in immuno-PET (Positron Emission Tomography) imaging. Clinically, the 89Zr4+ ion is introduced into antibodies by complexation with desferrioxamine B. However, producing complexes of limited kinetic inertness.

Synthesis, Characterization and In Vitro Evaluation of Hybrid Monomeric Peptides Suited for Multimodal Imaging by PET/OI: Extending the Concept of Charge-Cell Binding Correlation.

In the context of hybrid multimodal imaging agents for gastrin releasing peptide receptor (GRPR) targeting, a correlation between the net charge and the receptor affinity of the agents was recently found. In particular, a decrease in in vitro GRPR binding affinity was observed in case of an increasing number of negative charges for dually labeled GRPR-specific peptide dimers suited for positron emission tomography and optical imaging (PET/OI). This adverse influence of anionic charges could be in part compensated by a higher valency of peptide multimerization.

Design, Synthesis, In Vitro and In Vivo Evaluation of Heterobivalent SiFA-Modified Peptidic Radioligands Targeting Both Integrin αβ and the MC1 Receptor-Suitable for the Specific Visualization of Melanomas?

Combining two peptides addressing two different receptors to a heterobivalent peptidic ligand (HBPL) is thought to enable an improved tumor-targeting sensitivity and thus tumor visualization, compared to monovalent peptide ligands. In the case of melanoma, the Melanocortin-1 receptor (MC1R), which is stably overexpressed in the majority of primary malignant melanomas, and integrin αβ, which is involved in lymph node metastasis and therefore has an important role in the transition from local to metastatic disease, are important target receptors. Thus, if a radiolabeled HBPL could be developed that was able to bind to both receptor types, the early diagnosis and correct staging of the disease would be significantly increased.

PESIN Conjugates for Multimodal Imaging: Can Multimerization Compensate Charge Influences on Cell Binding Properties? A Case Study.

Recently, anionic charges were found to negatively influence the in vitro gastrin-releasing peptide receptor (GRPR) binding parameters of dually radioisotope and fluorescent dye labeled GRPR-specific peptide dimers. From this, the question arose if this adverse impact on in vitro GRP receptor affinities could be mitigated by a higher valency of peptide multimerization. For this purpose, we designed two different hybrid multimodal imaging units (MIUs), comprising either one or two click chemistry-compatible functional groups and reacted them with PESIN (PEG-BBN, PEG = polyethylene glycol) dimers to obtain a dually labeled peptide homodimer or homotetramer.

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, characterization and optimization of in vitro properties of NIR-fluorescent cyclic α-MSH peptides for melanoma imaging.

Melanoma are malignant tumors derived from melanocytes being responsible for the majority of skin cancer deaths with an increasing rate of incidence. The Melanocortin-1 receptor (MC1R) has been recognized as a molecular target for melanoma detection. Here, we report on the development and optimization of molecular probes which are based on novel conjugates of near-infrared (NIR) fluorescent indocyanine dyes and an MC1R-targeting peptide intended for optical fluorescence imaging enabling an early, specific, accurate and sensitive diagnosis of malignant melanomas.

Hybrid Multimodal Imaging Synthons for Chemoselective and Efficient Biomolecule Modification with Chelator and Near-Infrared Fluorescent Cyanine Dye.

The development of hybrid multimodal imaging synthons (MIS), carrying in addition to a chelator for radiometal labeling also a near-infrared (NIR) fluorescent cyanine dye was the aim of this work. The MIS should be introducible into biomolecules of choice via an efficient and chemoselective click chemistry reaction. After chemical optimization, a successful synthetic strategy towards such hybrid MIS was developed, based on solid phase-based synthesis techniques and applying different near-infrared fluorescent cyanine dyes.

Total Synthesis and Structural Assignment of Curvicollide C.

The first total synthesis of (+)-curvicollide C has been accomplished. Cross-metathesis and Julia-Kocienski olefination were instrumental in the synthesis of 1,3-diene segments and allowed for a ternary-convergent synthetic design. A full structural assignment is proposed for (-)-curvicollide C, a uniquely structured polyketide of fungal origin.

Catalytic asymmetric Claisen rearrangement of Gosteli-type allyl vinyl ethers: total synthesis of (-)-9,10-dihydroecklonialactone B.

The enantioselective synthesis of (-)-9,10-dihydroecklonialactone B is described. The catalytic asymmetric Claisen rearrangement of a Gosteli-type allyl vinyl ether was utilized to afford an acyclic α-keto ester building block endowed with functionality amenable to the preparation of the carbocyclic target molecule by suitable postrearrangement transformations: A highly diastereoselective Corey-Bakshi-Shibata reduction of a β-chiral α-keto ester and a reductive homologation of an α-hydroxy ester. A transprotection tactic by a chemoselective intramolecular 6-exo-trig iodoetherification enabled regioselective ring-closing alkene metatheses to afford the 5- as well as the 14-membered ring, however, with mixed success in terms of E/Z selectivity.

Total synthesis of (-)-ecklonialactone B.

The total synthesis of (-)-ecklonialactone B as well as the 9,10-dihydro derivative by two different strategies is reported. The catalytic asymmetric Claisen rearrangement of Gosteli-type allyl vinyl ethers delivered elaborated α-keto ester building blocks. Ring-closing metatheses, including a notable diastereotopos-differentiating variant, a B-alkyl Suzuki-Miyaura cross-coupling reaction and a regio- and diastereoselective last-step epoxidation are key contributors.