The authors wish to replace the 'Author Contributions' statement and the affiliation for Jochen Maurer of this article [...
View Article and Find Full Text PDFNeural stem cells (NSCs) present attractive natural drug delivery systems (DDSs). Their migratory potential enables crossing of the blood-brain barrier and efficient and selective accumulation near malignant cells. Here, we present the potential of NSCs as DDSs for nucleoside analogue-conjugated nanogels (NGs).
View Article and Find Full Text PDF[ F]FTC-146 was introduced as a very potent and selective sigma-1 receptor radioligand, which has shown promising application as an imaging agent for neuropathic pain with positron emission tomography. In line with a multi-laboratory project on animal welfare, we chose this radioligand to investigate its potential for detecting neuropathic pain and tissue damage in tumor-bearing animals. However, the radiochemical yield (RCY) of around 4-7% was not satisfactory to us, and efforts were made to improve it.
View Article and Find Full Text PDFBackground: Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCA).
View Article and Find Full Text PDFPARP1 inhibitors (PARPi) are currently approved for BRCA metastatic breast cancer, but they have shown limited response in triple negative breast cancer (TNBC) patients. Combination of an Auger emitter with PARPis enables PARP inhibition and DNA strand break induction simultaneously. This will enhance cytotoxicity and additionally allow a theranostic approach.
View Article and Find Full Text PDFEur J Nucl Med Mol Imaging
August 2022
Purpose: Kidney fibrosis leads to a progressive reduction in kidney function ultimately resulting in kidney failure. Diagnostic tools to detect kidney fibrosis are all invasive in nature requiring kidney biopsies with subsequent histological validation. In this retrospective study, the diagnostic value of three different radiotracers for the noninvasive prediction of kidney fibrosis was analyzed, taking into account the glomerular filtration rate (GFR) and the intra-renal parenchymal radiotracer uptake.
View Article and Find Full Text PDFOver the past 20 years, Ga-labelled radiopharmaceuticals have become an important part in clinical routine. However, the worldwide supply with Ge/Ga generators is limited as well as the number of patient doses per batch of Ga radiopharmaceutical. In the recent years, a new technique appeared, making use of the ease of aqueous labelling via chelators as with Ga but using F instead.
View Article and Find Full Text PDFGiven the high sensitivity and specificity of sodium [F]Fluoride (Na[F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet.
View Article and Find Full Text PDFBackground: Personalized molecular radiotherapy based on theragnostics requires accurate quantification of the amount of radiopharmaceutical activity administered to patients both in diagnostic and therapeutic applications. This international multi-center study aims to investigate the clinical measurement accuracy of radionuclide calibrators for 7 radionuclides used in theragnostics: Tc, In, I, I, I, Lu, and Y.
Methods: In total, 32 radionuclide calibrators from 8 hospitals located in the Netherlands, Belgium, and Germany were tested.
Background: Lumbar disc herniation is often associated with an inflammatory process. In this context, inflammation has been considered a key factor in the modulation of pain. Here, we present a case of inflammatory activity directly documented in a patient with a lumbar disc herniation.
View Article and Find Full Text PDFPurpose: The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development.
Results: Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients.
Background: Triple-negative breast cancer has extremely high risk of relapse due to the lack of targeted therapies, intra- and inter-tumoral heterogeneity, and the inherent and acquired resistance to therapies. In this study, we evaluate the potential of prostate-specific membrane antigen (PSMA) as target for radio-ligand therapy (RLT).
Methods: Tube formation was investigated after incubation of endothelial HUVEC cells in tumor-conditioned media and monitored after staining using microscopy.
Aim: In metastatic prostate cancer patients PSMA targeting radioligands have gained significant impact as theranostic probes. In this study a correlation between total tumor volume (TTV) and measured kidney dose as well as salivary glands (SG) uptake in Lu-PSMA-617 therapy was evaluated.
Methods: Eleven consecutive prostate cancer patients receiving a first cylcle of Lu-PSMA-617 (administered activity of approximately 6GBq) were included.
Triple-negative breast cancer has an extremely high rate of relapse. This is particularly due to the existence and survival of cancer stem cells (CSCs) characterized by increased amounts of glutathione (GSH). In this study, we evaluated the potential of pharmacological GSH depletion to sensitize CSCs to ionizing radiotherapy with an I-125-labeled nucleoside analog, 5-iodo-4'-thio-2'-deoxyuridine (ITdU).
View Article and Find Full Text PDFHere, we examined the potential of blocking the thymidine de novo synthesis pathways for sensitizing melanoma cells to the nucleoside salvage pathway targeting endogenous DNA irradiation. Expression of key nucleotide synthesis and proliferation enzymes thymidylate synthase (TS) and thymidine kinase 1 (TK1) was evaluated in differentiated (MITF [microphthalmia-associated transcription factor] IGR1) and invasive (MITF IGR37) melanoma cells. For inhibition of de novo pathways cells were incubated either with an irreversible TS inhibitor 5-fluoro-2'-deoxyuridine (FdUrd) or with a competitive dihydrofolate-reductase (DHFR) inhibitor methotrexate (MTX).
View Article and Find Full Text PDFCyclooxygenase-2 (COX-2) is an important biomarker in several tumors. Available imaging probes display relatively low tumor to background ratios (smaller than 2:1). We evaluated newly developed indomethacin (Ind) derivatives for in vivo molecular imaging of COX-2 expressing carcinoma.
View Article and Find Full Text PDFAs the size of nanoparticles (NPs) is in the range of biological molecules and subcellular structures, they provide new perspectives in biomedicine. This work presents studies concerning the cellular uptake and distribution of phosphine-stabilized cytotoxic 1.4 nm sized AuNPs and their probable degradation during this process.
View Article and Find Full Text PDFPurpose: To examine the relationship between the extent of disease determined by [(68)Ga]PSMA-HBED-CC-PET/CT and the important clinical measures prostate-specific antigen (PSA), PSA doubling time (PSAdt) and Gleason score.
Methods: We retrospectively studied the first 155 patients with recurrent prostate cancer (PCA) referred to our university hospital for [(68)Ga]PSMA-HBED-CC PET/CT.
Results: PET/CT was positive in 44%, 79% and 89% of patients with PSA levels of ≤1, 1-2 and ≥2 ng/ml, respectively.
Purpose: To determine the frequency of seemingly pathological retroperitoneal uptake in the location of the coeliac ganglia in patients undergoing [(68)Ga]PSMA-HBED PET/CT.
Methods: The study included 85 men with prostate cancer referred for [(68)Ga]PSMA-HBED PET/CT. The PET/CT scans were evaluated for the local finding in the prostate and the presence of lymph node metastases, distant metastases and coeliac ganglia.
The [(18)F]fluoroethyl moiety has been widely utilized in the synthesis of (18)F-labelled compounds. The aim of this work was the reliable synthesis of [(18)F]FEtOTf with a novel strategy to increase the reactivity of the commonly used [(18)F]FEB and [(18)F]FEtOTos. [(18)F]FEtOTf and the intermediate [(18)F]FEtOH were synthesized in high RCY (78% and 85%, respectively) and purified by SPE.
View Article and Find Full Text PDFIn the insulin resistant heart, energy fuel selection shifts away from glucose utilization towards almost complete dependence on long-chain fatty acids (LCFA). This shift results in excessive cardiac lipid accumulation and eventually heart failure. Lipid-induced cardiomyopathy may be averted by strategies that increase glucose uptake without elevating LCFA uptake.
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