Technical note: Quantifying radionuclide residues in hospital wastewater: A case study on [I]I and [Lu]Lu/[Lu]Lu.

Background: Historically, [I]I has been a common isotope in radionuclide therapy, with [Lu]Lu-labelled radiopharmaceuticals now seeing a surge in use. These can include no-carrier-added or carrier-added [Lu]Lu with slight impurities of [Lu]Lu with a significantly longer half-life than [I]I. Wastewater from therapy wards can contain a mixture of these radioisotopes.

Technical note: Assessment of radiation measurement devices for the detection of [ Lu]Lu-labeled radiopharmaceuticals containing [ Lu]Lu-impurities.

Background: Nuclear medicine therapies using [ Lu]Lu-labeled radiopharmaceuticals have increased significantly in recent years. Some of these radiopharmaceuticals contain long-lived impurities of [ Lu]Lu. Identification of this specific contamination and its quantification is important in different scenarios.

Anatomical MRI and [F]FDG PET/CT imaging of Schistosoma mansoni in a NMRI mouse model.

Schistosomiasis represents one of the most devastating worm parasitosis in the world. Current diagnostic methods are insufficient to determine the infection grade and the disease related organ damage. We herein investigated whether discrimination of infection grade and its correlation to liver damage could be accurately performed by multimodal imaging in a mouse model of Schistosoma mansoni infection.

[F]fallypride-PET/CT Analysis of the Dopamine D₂/D₃ Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection.

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson's disease. The caudate-putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D₂/D₃ receptor (D₂/D₃R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection.

Antifibrogenic effects of vitamin D derivatives on mouse pancreatic stellate cells.

Aim: To study the molecular effects of three different D-vitamins, vitamin D2, vitamin D3 and calcipotriol, in pancreatic stellate cells (PSCs).

Methods: Quiescent PSCs were isolated from mouse pancreas and activated by seeding on plastic surfaces. The cells were exposed to D-vitamins as primary cultures (early-activated PSCs) and upon re-culturing (fully-activated cells).

[Ga]pentixafor for CXCR4 imaging in a PC-3 prostate cancer xenograft model - comparison with [F]FDG PET/CT, MRI and receptor expression.

Purpose: The aim was to characterize the properties of [Ga]Pentixafor as tracer for prostate cancer imaging in a PC-3 prostate cancer xenograft mouse model and to investigate its correlation with [F]FDG PET/CT, magnetic resonance imaging (MRI) and analyses.

Methods: Static [Ga]Pentixafor and [F]FDG PET as well as morphological/ diffusion weighted MRI and H MR spectroscopy was performed. Imaging data were correlated with biodistribution and CXCR4 expression in PC-3 tumors (immunohistochemistry (IHC), mRNA analysis).

Application of imaging techniques to monitor therapeutic efficiency of PLX4720 in an experimental model of microsatellite instable colorectal cancer.

Objectives: Patient-derived tumor cell lines are a powerful tool to analyze the sensitivity of individual tumors to specific therapies in mice. An essential prerequisite for such an approach are reliable quantitative techniques to monitor tumor progression .

Methods: We have employed HROC24 cells, grown heterotopically in NMRI Foxn1 mice, as a model of microsatellite instable colorectal cancer to investigate the therapeutic efficiencies of 5'-fluorouracil (5'-FU) and the mutant BRAF inhibitor PLX4720, a vemurafenib analogue, by three independent methods: external measurement by caliper, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-(F)fluoro-D-glucose (F-FDG).

A unique matched quadruplet of terbium radioisotopes for PET and SPECT and for α- and β- radionuclide therapy: an in vivo proof-of-concept study with a new receptor-targeted folate derivative.

Unlabelled: Terbium offers 4 clinically interesting radioisotopes with complementary physical decay characteristics: (149)Tb, (152)Tb, (155)Tb, and (161)Tb. The identical chemical characteristics of these radioisotopes allow the preparation of radiopharmaceuticals with identical pharmacokinetics useful for PET ((152)Tb) and SPECT diagnosis ((155)Tb) and for α- ((149)Tb) and β(-)-particle ((161)Tb) therapy. The goal of this proof-of-concept study was to produce all 4 terbium radioisotopes and assess their diagnostic and therapeutic features in vivo when labeled with a folate-based targeting agent.

Radioiodinated folic acid conjugates: evaluation of a valuable concept to improve tumor-to-background contrast.

Folic acid radioconjugates can be used for targeting folate receptor positive (FR(+)) tumors. However, the high renal uptake of radiofolates is a drawback of this strategy, particularly with respect to a therapeutic application due to the risk of damage to the kidneys by particle radiation. The goal of this study was to develop and evaluate radioiodinated folate conjugates as a novel class of folate-based radiopharmaceuticals potentially suitable for therapeutic application.

The low-energy β(-) and electron emitter (161)Tb as an alternative to (177)Lu for targeted radionuclide therapy.

Introduction: The low-energy β(-) emitter (161)Tb is very similar to (177)Lu with respect to half-life, beta energy and chemical properties. However, (161)Tb also emits a significant amount of conversion and Auger electrons. Greater therapeutic effect can therefore be expected in comparison to (177)Lu.

L1-CAM-targeted antibody therapy and (177)Lu-radioimmunotherapy of disseminated ovarian cancer.

The L1-cell adhesion molecule (L1-CAM) is highly expressed in various cancer types including ovarian carcinoma but is absent from most normal tissue. A chimeric monoclonal antibody, chCE7, specifically binds to human L1-CAM and exhibits anti-proliferative effects on L1-CAM-expressing tumor cells. The goal of this study was to evaluate the efficacy of a novel (177)Lu-chCE7 radioimmunotherapeutic agent and to compare it to a treatment protocol with unlabeled, growth-inhibiting chCE7 in a mouse xenograft model of disseminated ovarian cancer.

Radiolabeling of rituximab with (188)Re and (99m)Tc using the tricarbonyl technology.

Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20(+) B-cell tumors. Rituximab radiolabeled with β(-) emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the (99m)Tc- and (188)Re-tricarbonyl core (IsoLink technology).

A "click chemistry" approach to the efficient synthesis of multiple imaging probes derived from a single precursor.

Different imaging modalities can provide complementary information on biological processes at the cellular or molecular level in vitro and in vivo. However, specific molecular probes suitable for a comparison of different imaging modalities are often not readily accessible because their preparation is usually accomplished by individually developed and optimized syntheses. Herein, we present a general, modular synthetic approach that provides access to multiple probes derived from a single precursor by application of the same, efficient functionalization strategy, the Cu(I)-catalyzed cycloaddition of terminal alkynes and azides (click chemistry).

Evaluation of anti-VEGFR-3 specific scFv antibodies as potential therapeutic and diagnostic tools for tumor lymph-angiogenesis.

Vascular endothelial growth factor receptor-3 (VEGFR-3) plays a major role in lymph-angiogenesis, tumor growth and metastatic tumor cell dissemination. The receptor is over-expressed on lymphatic vessels in the vicinity of tumors and on the tumor vasculature and therefore may be an excellent target for an effective cancer intervention. We generated and characterized single chain antibody fragments (scFv) recognizing VEGFR-3 by phage display technology and expression in P.

Preclinical evaluation of novel organometallic 99mTc-folate and 99mTc-pteroate radiotracers for folate receptor-positive tumour targeting.

Purpose: The folate receptor (FR) is a valuable tumour marker, since it is frequently overexpressed on various cancer types. The purpose of the present study was to pre-clinically evaluate novel site-specifically modified (99m)Tc(CO)(3) folate (gamma-derivative 4, alpha-derivative 5) and pteroate (6) conjugates for FR targeting.

Methods: The (99m)Tc(CO)(3) radiotracers 4-6 were prepared by a kit-like procedure.

Double-stabilized neurotensin analogues as potential radiopharmaceuticals for NTR-positive tumors.

Introduction: Overexpression of neurotensin (NT) receptors in exocrine pancreatic cancer and other neuroendocrine cancers make them interesting targets for tumor imaging and therapy. Modifications at the cleavage bonds 8-9 and 11-12 led to the synthesis of NT-XII, NT-XIII and NT-XVIII, three new stabilized analogues. (NalphaHis)Ac was coupled to the N-terminus for labeling with [(99m)Tc]-tricarbonyl.

Radiosynthesis and evaluation of two novel 123I-labeled 2-methyl-4-nitroimidazole derivatives as potential infection imaging agents.

Introduction: The inflammation- and infection-seeking properties of (131)I-labeled ornidazole, a 5-nitroimidazole derivative, have recently been reported. Whole-body images in rabbits showed a more rapid uptake in inflamed areas compared to (67)Ga. In the present study, two novel (123)I-labeled 2-methyl-4-nitroimidazole derivatives were synthesized and their infection-seeking properties compared with those of (67)Ga and (123)I-labeled ornidazole.