The synthesis of ,1,4-tri(alkoxy-hydroxybenzyl)-1,4-diazepane-amines: investigations on reaction characteristics and mechanism.

1,4-Diazepane-6-amine (DAZA) can be alkylated with three 2-hydroxybenzyl pendant arms, resulting in hexadentate chelators suitable for coordination of radiometals like Ga. These chelators, ,1,4-tri(alkoxy-2-hydroxybenzyl)-DAZA, can be produced via a one-pot synthesis, with the first step being a carbonyl amine condensation of DAZA with two respective 4-alkoxy-2-hydroxybenzaldehydes, followed by reductive amination with sodium borohydride. While the first step of this reaction is predictable, the subsequent reductive amination can result in either mono-, di- or tri(alkoxy-hydroxybenzyl)-DAZA compounds.

Radionuclide Cisternography with [Cu]Cu-DOTA.

Radionuclide cisternography (RNC) is a method for conducting imaging of the cerebrospinal system and can be used to identify cerebrospinal fluid leaks. So far, RNC has commonly employed radiopharmaceutical agents suitable only for single-photon emission tomography techniques, which are thus lacking in terms of image resolution and can potentially lead to false-negative results. Therefore, [Cu]Cu-DOTA was investigated as an alternative radiopharmaceutical for RNC, employing positron emission tomography (PET) instead of single-photon emission tomography.

A Novel Breast Cancer Xenograft Model Using the Ostrich Chorioallantoic Membrane-A Proof of Concept.

The avian chorioallantoic membrane (CAM) assay has attracted scientific attention in cancer research as an alternative or complementary method for in vivo animal models. Here, we present a xenograft model based on the ostrich ( CAM assay for the first time. The engraftment of 2 × 10 breast cancer carcinoma MDA-MB-231 cells successfully lead to tumor formation.

67 Ga-PSMA I&T for Radioguided Surgery of Lymph Node Metastases in Patients With Biochemical Recurrence of Prostate Cancer.

Purpose: Radioguided lymph node dissection in patients with prostate cancer, and suffering from biochemical recurrence has been described thoroughly during the past few years. Several prostate-specific membrane antigen (PSMA)-directed ligands labeled with 111 In, 99m Tc, and 68 Ga have been published; however, limitations regarding availability, short half-life, high costs, and unfavorable high energy might restrict frequent use. This study aims at introducing 67 Ga as a promising radionuclide for radioguided surgery.

Liver PET Reloaded: Automated Synthesis of [Ga]Ga-BP-IDA for Positron Imaging of the Hepatobiliary Function and First Clinical Experience.

Hepatobiliary scintigraphy is a well-established nuclear imaging method for evaluating liver function and displaying the biliary system, but the spatial and temporal resolution is limited, and, there is still no established PET equivalent. Adapted from the work of Schuhmacher et al. in 1983, the production of a Gallium-labeled substitute, tetrabromophthalein ([Ga]Ga-BP-IDA), was undertaken according to current Good Manufacturing Practice (GMP) standards and proved feasible and reproducible.

Preparation and labelling of red blood cells with [Ga]Ga-oxine for PET/CT imaging of the human spleen.

Introduction: With the introduction of automated synthetization methods, the in-house production of several Ga-based tracers became feasible in hospital laboratories. We describe a possible standard operating procedure (SOP) for [Ga]Ga-oxine-labeled heat-denaturated erythrocytes, which can be used for selective imaging in patients with splenic disorders.

Methods: Heat-denaturated erythrocytes were labeled with [Ga]Ga-oxine, which was produced from Ga and 8-hydroxyquinoline on an automated synthesizer.

PET/CT of the Spleen with Gallium-Oxine-Labeled, Heat-Damaged Red Blood Cells: Clinical Experience and Technical Aspects.

Several scintigraphic techniques have been supplemented or replaced by PET/CT methods because of their superior sensitivity, high resolution, and absolute activity quantification capability. The purpose of this project was the development of a PET tracer for splenic imaging, its radiopharmaceutical validation, and its application in selected patients in whom unclear constellations of findings could not be resolved with established imaging methods. Heat-damaged red blood cells (RBCs) were labeled with [Ga]gallium-oxine, which was produced from [Ga]gallium and 8-Hydroxyquinoline (oxine) on an automated synthesizer.

Automated GMP Production and Preclinical Evaluation of [Ga]Ga-TEoS-DAZA and [Ga]Ga-TMoS-DAZA.

[Ga]Ga-TEoS-DAZA and [Ga]Ga-TMoS-DAZA are two novel radiotracers suitable for functional PET liver imaging. Due to their specific liver uptake and biliary excretion, the tracers may be applied for segmental liver function quantification, gall tree imaging and the differential diagnosis of liver nodules. The purpose of this study was to investigate problems that occurred initially during the development of the GMP compliant synthesis procedure and to evaluate the tracers in a preclinical model.

In-ovo imaging using ostrich eggs: Biomagnetism for detection of cardiac signals and embryonal motion.

In-ovo imaging using ostrich eggs has been described as a potential alternative to common animal testing. The main advantage is its independence from small animal imaging devices as ostrich eggs provide good image quality on regular CT, MRI, or PET used in examinations of humans. However, embryonal motion during dynamic imaging studies produce artifacts.

Differences in Distribution and Detection Rate of the [Ga]Ga-PSMA Ligands PSMA-617, -I&T and -11-Inter-Individual Comparison in Patients with Biochemical Relapse of Prostate Cancer.

The biochemical relapse of prostate cancer is diagnostically challenging but of high clinical impact for subsequent patient treatment. PET/CT with radiolabeled PSMA ligands outperforms conventional diagnostic methods in the detection of tumor recurrence. Several radiopharmaceuticals were and are available for use.

Ectopic Retrolaryngeal Parathyroid Adenoma Detected by 18F-Ethylcholine PET/US Fusion Imaging.

A 68-year-old woman was referred with the diagnosis of symptomatic pHPT (primary hyperparathyroidism). Ultrasonography (US) and 99mTc-MIBI scintigraphy could not clearly identify a parathyroid adenoma. A primary unilateral surgical exploration remained unsuccessful to remove adenomatous parathyroid tissue and the pHPT persisted.

Hepatobiliary Excretion PET/CT With 68Ga-TAoS-DAZA to Evaluate Bile Duct Patency.

Tri-alkoxysalicyl-1,4-diazepan-6-amine (TAoS-DAZA) ligands, radiolabelled with 68Ga, have been proposed as PET/CT agents for depiction and quantification of hepatobiliary function and evaluation of bile excretion. In the presented case, a patient with hepatocellulary carcinoma underwent PET/CT with the TAoS-derivate 68Ga-tri-methoxysalicyl-(TMoS)-DAZA to determine the patency of intrahepatic and extrahepatic bile ducts, in particular of a stent in the common bile duct. The PET/CT was performed without complications.

Dynamic PET/CT with the Hepatobiliary Tracer [68Ga]Ga-Tmos-DAZA for Characterization of a Hepatic Tumor.

Established imaging modalities for the characterization of liver tumors are computed tomography (CT), magnetical resonance (MR) imaging, sonography, and hepatobiliary scintigraphy. In some cases, their results may be inconclusive or certain examinations not possible due to contraindications. Positron emission tomography (PET)/CT has the capability of dynamic imaging with high temporal resolution.

Design and practical evaluation of a shielded application system for intravenously administered radionuclide therapies.

Aim:  Intravenous radionuclide therapies are gaining importance. With the increased frequency of these therapies, safe application procedures in combination with effective radiation protection are needed. We present a shielded system which can be universally used for the application of liquid radiopharmaceuticals.

Metal-Based Complexes as Pharmaceuticals for Molecular Imaging of the Liver.

This article reviews the use of metal complexes as contrast agents (CA) and radiopharmaceuticals for the anatomical and functional imaging of the liver. The main focus was on two established imaging modalities: magnetic resonance imaging (MRI) and nuclear medicine, the latter including scintigraphy and positron emission tomography (PET). The review provides an overview on approved pharmaceuticals like Gd-based CA and Tc-based radiometal complexes, and also on novel agents such as Ga-based PET tracers.

N,1,4-Tri(4-alkoxy-2-hydroxybenzyl)-DAZA: efficient one-pot synthesis and labelling with Ga for PET liver imaging in ovo.

We report the isolation of a new type of 1,4-diazepan-6-amine (DAZA)-based ligand. Condensation of aldehydes with DAZA gives a novel class of 1,5-diazabicyclo[3.2.

Investigations on the Ga(III) Complex of EOB-DTPA and Its 68Ga Radiolabeled Analogue.

We demonstrate a method for the isolation of EOB-DTPA (3,6,9-triaza-3,6,9-tris(carboxymethyl)-4-(ethoxybenzyl)-undecanedioic acid) from its Gd(III) complex and protocols for the preparation of its novel non-radioactive, i.e., natural Ga(III) as well as radioactive (68)Ga complex.