Preparation and preclinical evaluation of a Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me.

Background: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of Ga- and Cu-based radiopharmaceuticals. Here, a Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the αß-targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of Ga-labelled radiotracers.

The somatostatin receptor 2 antagonist 64Cu-NODAGA-JR11 outperforms 64Cu-DOTA-TATE in a mouse xenograft model.

Copper-64 is an attractive radionuclide for PET imaging and is frequently used in clinical applications. The aim of this study was to perform a side-by-side comparison of the in vitro and in vivo performance of 64Cu-NODAGA-JR11 (NODAGA = 1,4,7-triazacyclononane,1-glutaric acid,4,7-acetic acid, JR11 = p-Cl-Phe-cyclo(D-Cys-Aph(Hor)-D-Aph(cbm)-Lys-Thr-Cys)D-Tyr-NH2), a somatostatin receptor 2 antagonist, with the clinically used sst2 agonist 64Cu-DOTA-TATE ((TATE = D-Phe-cyclo(Cys-Tyr-D-Trp-Lys-Thr-Cys)Thr). In vitro studies demonstrated Kd values of 5.

In vitro and in vivo evaluation of the bifunctional chelator NODIA-Me in combination with a prostate-specific membrane antigen targeting vector.

Introduction: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three five-membered azaheterocyclic arms for complexation of the PET nuclides gallium-68 and copper-64. The main objective of this study was to evaluate the stability and pharmacokinetics of Ga- and Cu-complexes of the bifunctional chelator NODIA-Me 1 covalently bound to a PSMA targeting vector in vivo.

Methods: NODIA-Me 1 was conjugated to the PSMA targeting Glu-NH-CO-NH-Lys moiety to give the bioconjugate NODIA-Me-NaI-Ahx-PSMA 4.

Radiochemistry and Preclinical PET Imaging of Ga-Desferrioxamine Radiotracers Targeting Prostate-Specific Membrane Antigen.

Radiotracers incorporating the urea-based Glu-NH-C(O)-NH-Lys group have gained prominence due to their role in targeting prostate-specific membrane antigen (PSMA)-a clinical biomarker of prostate cancer. Here, the synthesis, radiolabeling, and in vitro and in vivo characterization of two Ga-radiolabeled Glu-NH-C(O)-NH-Lys radiotracers conjugated to the desferrioxamine B (DFO) chelate were evaluated. Two linker groups based on amide bond and thiourea coupling chemistries were employed to develop Ga-DFO-Nsucc-PSMA (Ga-4) and Ga-DFO- pNCS-Bn-PSMA (Ga-7), respectively.

Gallium Complexation, Stability, and Bioconjugation of 1,4,7-Triazacyclononane Derived Chelators with Azaheterocyclic Arms.

We have recently introduced a 1,4,7-triazacyclononane (TACN) based chelating system with additional five-membered azaheterocyclic substituents for complexation of radioactive Cu ions. In this work, we investigated the complexation properties of these novel chelators with Ga. In labeling experiments, we could show that the penta- and hexadentate imidazole derivatives NODIA-Me 4 and NOTI-Me 1 can be labeled with Ga in specific activities up to ∼30 MBq nmol, while the corresponding thiazole derivative NOTThia 2 did not label satisfactorily under identical conditions.

Chronic lymphocytic leukemia-associated chromosomal abnormalities and miRNA deregulation.

Chronic lymphocytic leukemia is the most common leukemia in adults. By cytogenetic investigations major subgroups of the disease can be identified that reflect different routes of tumor development. Of these chromosomal deviations, trisomy 12 and deletions of parts of either the long arm of chromosome 13, the long arm of chromosome 11, or the short arm of chromosome 17 are most commonly detected.

Interphase fluorescence in situ hybridization analysis detects a much higher rate of thyroid tumors with clonal cytogenetic deviations of the main cytogenetic subgroups than conventional cytogenetics.

In benign thyroid lesions, three main cytogenetic subgroups, characterized by trisomy 7 or structural aberrations involving either chromosomal region 19q13.4 or 2p21, can be distinguished by conventional cytogenetics (CC). As a rule, these aberrations seem to be mutually exclusive.