Quantitative accuracy of preclinical in ovo PET/MRI: influence of attenuation and quantification methods.

Aim: The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) provides an innovation leap in the use of fertilized chicken eggs (in ovo model) in preclinical imaging as PET/MRI enables the investigation of the chick embryonal organ-specific distribution of PET-tracers. However, hybrid PET/MRI inheres technical challenges in quantitative in ovo PET such as attenuation correction (AC) for the object as well as for additional hardware parts present in the PET field-of-view, which potentially contribute to quantification biases in the PET images if not accounted for. This study aimed to investigate the influence of the different sources of attenuation on in ovo PET/MRI and assess the accuracy of MR-based AC for in ovo experiments.

Preclinical evaluation of the potential PARP-imaging probe [carbonyl-C]DPQ.

Background: Poly (ADP-ribose) polymerase (PARP) enzymes are crucial for the repair of DNA single-strand breaks and have become key therapeutic targets in homologous recombination-deficient cancers, including prostate cancer. To enable non-invasive monitoring of PARP-1 expression, several PARP-1-targeting positron emission tomography (PET) tracers have been developed. Here, we aimed to preclinically investigate [carbonyl-C]DPQ as an alternative PARP-1 PET tracer as it features a strongly distinct chemotype compared to the frontrunners [F]FluorThanatrace and [F]PARPi.

The importance of radiochemical purity: Cellular binding and internalization of different radiometal chlorides in prostate cancer cells.

Radiometals play an important role in nuclear medicine, both for imaging and therapy. Binding studies represent an important step in the development of new radiolabeled ligands, as valuable insights into the binding properties can be gained. However, this technique requires high radiochemical purity, otherwise results may lead to wrong assumptions or misinterpretations of affinities or uptake rates.

Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103.

BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy.

Radiobiological Assessment of Targeted Radionuclide Therapy with [Lu]Lu-PSMA-I&T in 2D vs. 3D Cell Culture Models.

In vitro therapeutic efficacy studies are commonly conducted in cell monolayers. However, three-dimensional (3D) tumor spheroids are known to better represent in vivo tumors. This study used [Lu]Lu-PSMA-I&T, an already clinically applied radiopharmaceutical for targeted radionuclide therapy against metastatic castrate-resistant prostate cancer, to demonstrate the differences in the radiobiological response between 2D and 3D cell culture models of the prostate cancer cell lines PC-3 (PSMA negative) and LNCaP (PSMA positive).

Quality Assurance Investigations and Impurity Characterization during Upscaling of [Lu]Lu-PSMA.

[Lu]Lu-PSMA is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged.

Synthesis and Preclinical Evaluation of Radiolabeled [Ru]BOLD-100.

The first-in-class ruthenium-based chemotherapeutic agent BOLD-100 (formerly IT-139, NKP-1339, KP1339) is currently the subject of clinical evaluation for the treatment of gastric, pancreatic, colorectal and bile duct cancer. A radiolabeled version of the compound could present a helpful diagnostic tool. Thus, this study investigated the pharmacokinetics of BOLD-100 in more detail to facilitate the stratification of patients for the therapy.

A fingerprint of 2-[F]FDG radiometabolites - How tissue-specific metabolism beyond 2-[F]FDG-6-P could affect tracer accumulation.

Studies indicate that the radiotracer 2-[F]fluoro-2-deoxy-D-glucose (2-[F]FDG) can be metabolized beyond 2-[F]FDG-6-phosphate (2-[F]FDG-6-P), but its metabolism is incompletely understood. Most importantly, it remains unclear whether downstream metabolism affects tracer accumulation Here we present a fingerprint of 2-[F]FDG radiometabolites over time in cancer cells, corresponding tumor xenografts and murine organs. Strikingly, radiometabolites representing glycogen metabolism or the oxPPP correlated inversely with tracer accumulation across all examined tissues.

Direct Patlak Reconstruction of [Ga]Ga-PSMA PET for the Evaluation of Primary Prostate Cancer Prior Total Prostatectomy: Results of a Pilot Study.

To investigate the use of kinetic parameters derived from direct Patlak reconstructions of [Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) to predict the histological grade of malignancy of the primary tumor of patients with prostate cancer (PCa). Thirteen patients (mean age 66 ± 10 years) with a primary, therapy-naïve PCa (median PSA 9.3 [range: 6.

Synthesis of 4-Deoxy-4-Fluoro-d-Sedoheptulose: A Promising New Sugar to Apply the Principle of Metabolic Trapping.

Fluorinated carbohydrates are important tools for understanding the deregulation of metabolic fluxes and pathways. Fluorinating specific positions within the sugar scaffold can lead to enhanced metabolic stability and subsequent metabolic trapping in cells. This principle has, however, never been applied to study the metabolism of the rare sugars of the pentose phosphate pathway (PPP).

Mimicking Tumor Cell Heterogeneity of Colorectal Cancer in a Patient-derived Organoid-Fibroblast Model.

Background & Aims: Patient-derived organoid cancer models are generated from epithelial tumor cells and reflect tumor characteristics. However, they lack the complexity of the tumor microenvironment, which is a key driver of tumorigenesis and therapy response. Here, we developed a colorectal cancer organoid model that incorporates matched epithelial cells and stromal fibroblasts.

Sex-specific radiomic features of L-[S-methyl-C] methionine PET in patients with newly-diagnosed gliomas in relation to IDH1 predictability.

Introduction: Amino-acid positron emission tomography (PET) is a validated metabolic imaging approach for the diagnostic work-up of gliomas. This study aimed to evaluate sex-specific radiomic characteristics of L-[S-methyl-Cmethionine (MET)-PET images of glioma patients in consideration of the prognostically relevant biomarker isocitrate dehydrogenase (IDH) mutation status.

Methods: MET-PET of 35 astrocytic gliomas (13 females, mean age 41 ± 13 yrs.

Comparison of Radiation Response between 2D and 3D Cell Culture Models of Different Human Cancer Cell Lines.

Radiation therapy is one of the most effective tools in cancer therapy. However, success varies individually, necessitating improved understanding of radiobiology. Three-dimensional (3D) tumor spheroids are increasingly gaining attention, being a superior in vitro cancer model compared to 2D cell cultures.

Effects of bilateral sequential theta-burst stimulation on 5-HT receptors in the dorsolateral prefrontal cortex in treatment-resistant depression: a proof-of-concept trial.

Theta-burst stimulation (TBS) represents a brain stimulation technique effective for treatment-resistant depression (TRD) as underlined by meta-analyses. While the methodology undergoes constant refinement, bilateral stimulation of the dorsolateral prefrontal cortex (DLPFC) appears promising to restore left DLPFC hypoactivity and right hyperactivity found in depression. The post-synaptic inhibitory serotonin-1A (5-HT) receptor, also occurring in the DLPFC, might be involved in this mechanism of action.

CAM-Xenograft Model Provides Preclinical Evidence for the Applicability of [Ga]Ga-Pentixafor in CRC Imaging.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Increased expression of CXCR4 has been associated with liver metastasis, disease progression, and shortened survival. Using in vitro cell binding studies and the in ovo model, we aimed to investigate the potential of [Ga]Ga-Pentixafor, a radiotracer specifically targeting human CXCR4, for CRC imaging.

Response to [ 177 Lu]Lu-PSMA radioligand therapy in metastatic castration-resistant prostate cancer patients presenting with only lymph node metastases.

Objective: [ 177 Lu]Lu-PSMA radioligand therapy (PSMA-RLT) is a promising therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) and offers a survival benefit particularly to patients with only lymph node metastases. We therefore sought to evaluate the clinical outcome of this therapy in such a cohort.

Methods: Of all prostate cancer patients admitted to our department between September 2015 and March 2019 to receive 1-4 courses of PSMA-RLT (each course consisted of three cycles of highly standardized PSMA-RLT every 4 weeks), only 10 consecutive men were found to have nodal metastases only and were analyzed retrospectively.

Autoradiography on deparaffinized tissue sections - A feasibility study with Ga-labeled PET-tracers.

Tissue available for retrospective research questions is often already paraffin-embedded for better preservation. However, in vitro autoradiography (AURA) is normally performed on cryopreserved tissue sections. We hypothesized a) that it would also be feasible with deparaffinized tissue sections, enabling the use of human paraffin-embedded tissue for in vitro AURA and b) that the results would be comparable to those obtained with corresponding cryosections.

Biodistribution and dosimetry of the GluN2B-specific NMDA receptor PET radioligand (R)-[C]Me-NB1.

Background: The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission.

Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning.

Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury.

Feasibility and Optimal Time Point of [Ga]Gallium-labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography Imaging in Patients Undergoing Cytoreductive Surgery After Systemic Therapy for Primary Oligometastatic Prostate Cancer: Implications for Patient Selection and Extent of Surgery.

Background: Prostate-specific membrane antigen (PSMA) targeted molecular imaging using positron emission tomography (PET) has significantly improved the diagnosis and treatment of prostate cancer (PCA).

Objective: To assess the feasibility and compare the diagnostic accuracy of [Ga]Ga-PSMA-11 PET images taken at baseline, before the initiation of systemic treatment and preoperative images, using histopathology after cytoreductive surgery as reference.

Design Setting And Participants: We identified 20 patients in our prospectively maintained database with primary oligometastatic PCA who underwent cytoreductive radical prostatectomy and superextended pelvic lymph node dissection after systemic therapy, who had baseline and preoperative [Ga]Ga-PSMA-11 PET imaging available.

Cyclotrons Operated for Nuclear Medicine and Radiopharmacy in the German Speaking D-A-CH Countries: An Update on Current Status and Trends.

Background: Cyclotrons form a central infrastructure and are a resource of medical radionuclides for the development of new radiotracers as well as the production and supply of clinically established radiopharmaceuticals for patient care in nuclear medicine.

Aim: To provide an updated overview of the number and characteristics of cyclotrons that are currently in use within radiopharmaceutical sciences and for the development of radiopharmaceuticals to be used for patient care in Nuclear Medicine in Germany (D), Austria (A) and Switzerland (CH).

Methods: Publicly available information on the cyclotron infrastructure was (i) consolidated and updated, (ii) supplemented by selective desktop research and, last but not least, (iii) validated by members of the committee of the academic "Working Group Radiochemistry and Radiopharmacy" (AGRR), consisting of radiochemists and radiopharmacists of the D-A-CH countries and belonging to the German Society of Nuclear Medicine (DGN), as well as the Radiopharmaceuticals Committee of the DGN.