Lu-3BP-227 for Neurotensin Receptor 1-Targeted Therapy of Metastatic Pancreatic Adenocarcinoma: First Clinical Results.

Neurotensin receptor 1 (NTR1) is overexpressed in ductal pancreatic adenocarcinoma, which is still one of the deadliest cancers, with a very poor prognosis. Eligible patients were offered salvage radiopharmaceutical therapy with the novel NTR1 antagonist Lu-3BP-227. Six patients with confirmed ductal pancreatic adenocarcinoma who had exhausted all other treatment options received Lu-3BP-227 for evaluation of NTR1 expression in vivo.

First-in-Human PET/CT Imaging of Metastatic Neuroendocrine Neoplasms with Cyclotron-Produced Sc-DOTATOC: A Proof-of-Concept Study.

Sc is a promising positron emission tomography (PET) radionuclide (T = 4.04 hours, E = 632 keV) and can be made available, using a cyclotron production route, in substantial quantities as a highly pure product. Herein, the authors report on a first-in-human PET/CT study using Sc-DOTATOC prepared with cyclotron-produced Sc.

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results.

Unlabelled: We recently introduced the potent gastrin-releasing peptide receptor (GRPR) antagonist Ga-SB3 (Ga-DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt), showing excellent tumor localizing efficacy in animal models and in patients. By replacement of the C-terminal Leu-Met-NH dipeptide of SB3 by Sta-Leu-NH, the novel GRPR antagonist NeoBOMB1 was generated and labeled with different radiometals for theranostic use. We herein report on the biologic profile of resulting Ga-, In-, and Lu-NeoBOMB1 radioligands in GRPR-expressing cells and mouse models.

Radiolabeling of DOTA-like conjugated peptides with generator-produced (68)Ga and using NaCl-based cationic elution method.

Gallium-68 ((68)Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize (68)Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging.

177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy.

Unlabelled: The objective of this study was to analyze the safety and efficacy of the (177)Lu-labeled DOTAGA-based prostate-specific membrane antigen (PSMA) ligand (177)Lu-DOTAGA-(I-y)fk(Sub-KuE) ((177)Lu-PSMA) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Fifty-six mCRPC patients underwent PSMA radioligand therapy (RLT) with (177)Lu-PSMA. (68)Ga-PSMA-(N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid) ((68)Ga-PSMA) PET/CT was used for patient selection and follow-up after PSMA RLT.

68Ga- and 177Lu-Labeled PSMA I&T: Optimization of a PSMA-Targeted Theranostic Concept and First Proof-of-Concept Human Studies.

Unlabelled: On the basis of the high and consistent expression of prostate-specific membrane antigen (PSMA) in metastatic prostate cancer (PC), the goal of this study was the development, preclinical evaluation, and first proof-of-concept investigation of a PSMA inhibitor for imaging and therapy (PSMA I&T) for (68)Ga-based PET and (177)Lu-based endoradiotherapeutic treatment in patients with metastatic and castration-resistant disease.

Methods: PSMA I&T was synthesized in a combined solid phase and solution chemistry strategy. The PSMA affinity of (nat)Ga-/(nat)Lu-PSMA I&T was determined in a competitive binding assay using LNCaP cells.

Purification and labeling strategies for (68)Ga from (68)Ge/ (68)Ga generator eluate.

For successful labeling, (68)Ge/(68)Ga generator eluate has to be concentrated (from 10 mL or more to less than 1 mL) and to be purified of metallic impurities, especially Fe(III), and (68)Ge breakthrough. Anionic, cationic and fractional elution methods are well known. We describe two new methods: (1) a combined cationic-anionic purification and (2) an easy-to-use and reliable cationic purification with NaCl solution.

Simplified NaCl based (68)Ga concentration and labeling procedure for rapid synthesis of (68)Ga radiopharmaceuticals in high radiochemical purity.

A simple sodium chloride (NaCl) based (68)Ga eluate concentration and labeling method that enables rapid, high-efficiency labeling of DOTA conjugated peptides in high radiochemical purity is described. The method utilizes relatively few reagents and comprises minimal procedural steps. It is particularly well-suited for routine automated synthesis of clinical radiopharmaceuticals.

Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine based on a cartridge purification method.

Introduction: O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) is widely used as a positron emission tomography tracer for brain tumors. Usually, a high-performance liquid chromatography (HPLC) purification at the end of the two-step synthesis is applied. In this work, we report an automatic radiosynthesis of FET with a purification procedure based on standard cartridges.

Rhenium and 99m-technetium complexes of monosaccharide based tripodal triamines as potential radio imaging agents.

A synthetic pathway to new sugar containing tripodal triamines of the TAME type (1,1,1-tris(aminomethyl)ethane) is presented. The tripodal bromo substituted precursors Ac3Xyl-O-CH2C(CH2Br)3, Ac4Glc-O-CH2C(CH2Br)3 and Ac4Gal-O-CH2C(CH2Br)3 (2a-c) were obtained by glycosidation reaction of the fully acetylated glycopyranosides with pentaerythritol tribromide. Nucleophilic substitution to the corresponding azides with sodium azide and deprotection of the sugars, followed by hydrogenation reaction in the presence of PtO2 leads to the triamines Xyl-O-CH2C(CH2NH2)3, Glc-O-CH2C(CH2NH2)3 and Gal-O-CH2C(CH2NH2)3 (5a-c).

Synthesis and structure of novel sugar-substituted bipyridine complexes of rhenium and 99m-technetium.

Novel ligands have been obtained from the reaction of 4,4'-dibromomethyl-2,2'-bipyridine with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylthiol, 2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosylthiol or 2,3,4,6-tetra-O-acetyl-alpha-D-thioacetylmannopyranoside in which the sugar residues are thioglycosidically linked to the bipyridine in the 4,4'-position. Cleavage of the acetyl groups affords hydrophilic symmetric ligands with free hydroxyl groups. Reaction of the new glycoconjugated ligands (L) with [Re(CO)(5)Cl] yields fluorescent complexes of general formula [Re(L)(CO)(3)Cl], which were characterised by mass spectrometry, elemental analysis and (1)H and (13)C NMR, IR, UV/Vis and fluorescence spectroscopy.