Nuclear medicine and biology最新文献

Introduction: Radiolanthanides ¹³²La and ¹³⁵La form a promising chemically matched theranostic pair. With a half-life of 18.95 h, ¹³⁵La acts as the therapeutic isotope as it releases approximately 11 Auger electrons per decay, making it compatible with targeted Auger electron therapy (TAET), whereas ¹³²La with half-life of 4.58 h undergoes positron emission making it compatible with imaging via positron emission tomography (PET).

Methods: ^132/135La were produced via irradiation of natural barium targets (99.9 %) with 12.8 MeV protons. A two-step separation scheme using extraction chromatographic resin TK200 (50-100 μm) and cation exchange resin Dowex 50Wx4 (200-400 mesh) was designed. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify non-radioactive impurities in each fraction of the separation method. The distribution coefficients of La³⁺ in HNO₃ on the TK200 resin and on both Dowex 50Wx8 (200-400 mesh) and Dowex 50Wx4 resins in ammonium α-hydroxyisobutyrate (pH 4.8) were determined, respectively.

Results: This novel separation scheme allowed for reliable separation of [^132/135La]La³⁺ from the Ba²⁺ target material, resulting in a high radiochemical yield of 98.3 ± 2.1 % (n = 3) with the final elute being directly compatible with subsequent radiolabeling due to the use of ammonium α-hydroxyisobutyrate to eliminate steps in the radiopharmaceutical synthetic process.

Background: The ovary is an important female organ not only for pregnancy but also for the regulation of life activities via hormone release. Ovarian function is measured by blood hormone levels, but the hormone level reflects only the ovarian reserve and no other essential ovarian functions, such as nurturing and expelling follicles. Ovarian fibrosis is related to essential ovarian function; however, the existing methods for evaluating fibrosis are invasive. Ovarian fibrosis has been reported to be associated with mitochondrial function. We hypothesized that positron emission tomography (PET) imaging of mitochondria could be a new, non-invasive method for evaluating essential ovarian function. In this study, we investigated the age-related changes in ovarian fibrosis using the mitochondrial complex-I (MC-I) PET probe, 2-tert-butyl-4-chloro-5-{6-[2-(2-¹⁸F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([¹⁸F]BCPP-EF).

Results: Aged rats, whose ovary function decline, exhibited a higher uptake of [¹⁸F]BCPP-EF in the ovary than young rats, and this high uptake in aged rats was suppressed by mitoquinone, a superoxide scavenger. Increased [¹⁸F]BCPP-EF uptake in the ovary was associated with ovarian fibrosis, but not with AMH level which reflects the ovarian reserve. Furthermore, the measurement of MC protein levels showed that the protein levels of MC-I increased with age, whereas those of MC-V decreased.

Conclusions: This study demonstrated that [¹⁸F]BCPP-EF can detect age-related changes in essential ovarian function evaluated by ovarian fibrosis. Therefore, [¹⁸F]BCPP-EF-PET is a useful non-invasive method for evaluating essential ovarian functions and will contribute to basic research on ovarian aging as well as drug discovery targeting ovarian dysfunction.

Limited availability constrains the implementation of ²²⁵Ac, the most promising α emitter for targeted therapy, in clinical practice. Proton activation of ²²⁶Ra is one of few realistic solutions to this problem. We have therefore measured cross sections of relevant ²²⁶Ra(p,xn) nuclear reactions in the energy range of 12.0 to 17.2 MeV. The obtained results allowed us to deduce the yield of ²²⁴Ac, ²²⁵Ac, and ²²⁶Ac. The consequences of our data to predictions of production capacity and radionuclidic purity of ²²⁵Ac are thoroughly discussed, and their comparison with previous measurements and with the prediction of the TALYS 1.96 nuclear reaction model code run with default parameters are provided.

The role of mitochondrial complex I (MC-I) dysfunction is well-documented across a range of neurodegenerative disorders. Recently, a novel positron emission tomography (PET) radioligand, [¹⁸F]CNL02, has been synthesized to target MC-I. In this paper, we provide a comprehensive characterization of [¹⁸F]CNL02, using nonhuman primate as a model system. In the brain of a rhesus macaque, [¹⁸F]CNL02 demonstrated specific binding in regions expressing MC-I. All observed brain regions showed rapid kinetic profiles. Analysis of arterial plasma indicated a swift clearance of [¹⁸F]CNL02 from the bloodstream. Metabolite analysis identified two predominant radiometabolites in the plasma. The regional brain time-activity curves (TACs) for [¹⁸F]CNL02 were effectively characterized through a two-tissue compartment model (2TCM). Furthermore, the total distribution volume was reliably estimated employing the Logan plot method. Consequently, continued development and refinement of [¹⁸F]CNL02 are imperative.

Introduction: Folate receptors (FR) have been considered a convenient target for different radiopharmaceuticals in recent years. Multifarious ⁶⁸Ga-labeled folate conjugates have been proposed as promising agents for the PET imaging of FR-overexpressing malignant neoplasms. In addition, radiolabeled folate-based conjugates can be effective for imaging non-tumor pathological foci characterized by a pronounced cluster of activated macrophages. We previously reported that a conjugate of folic acid with the NODAGA-chelator, labeled with gallium-68 and containing a (His-Glu)₂-tag ([⁶⁸Ga]Ga-NODAGA-[Lys-(HE)₂]-folic acid), is suitable for imaging tumor lesions characterized by an increased density of FR. Introduction of the (His-Glu)₂-tag into the structure of the folate radioconjugate significantly reduced its accumulation in non-target tissues (e.g., kidneys), leaving the accumulation in tumors at least at the same level, and even increasing it. The present study assessed the suitability of the developed molecule (in comparison with the unmodified analog) for imaging foci of non-oncological etiology characterized by a pronounced macrophage response.

Methods: Systemic juvenile idiopathic arthritis (JIA), reproduced in Wistar rats, was used as the pathology model. Acute inflammatory processes of soft tissues of septic and aseptic etiologies were selected as differential models.

Results: The results obtained in this study showed a significantly elevated level of accumulation in the JIA focus compared to healthy rat paws and accumulation in the foci of differential models of the inflammatory process, which confirms the macrophage-mediated pathway of accumulation of the studied compounds. Simultaneously, the ratio of accumulation in pathology to accumulation in comparable healthy tissues in all studied pathologies was significantly high.

Conclusion: The data obtained allowed us to conclude the diagnostic potential of new radiolabeled folate-based conjugate with (His-Glu)₂-tag for pharmacokinetic property optimization in the radionuclide diagnosis of rheumatoid and other diseases characterized by a pronounced macrophage immune response. The mathematical compartment model quantitatively confirmed that the additional (His-Glu)₂ fragment introduced in the molecule acts in favor of potential radiopharmaceutical use to visualize inflammatory processes by positron emission tomography.

Targeted Alpha Therapy has shown great promise in cancer treatment, sparking significant interest over recent decades. However, its broad adoption has been impeded by the scarcity of alpha-emitters and the complexities related to their use. The availability of these radionuclides is often constrained by the intricate production processes and purification, as well as regulatory and logistical challenges. Moreover, the high cost and technical difficulties associated with handling and applying alpha-emitting radionuclides pose additional barriers to their clinical implementation. This Alpha Atlas provides an in-depth overview of the leading alpha-particle emitting radionuclide candidates for clinical use, focusing on their production processes and supply chains. By mapping the current facilities that produce and supply these radionuclides, this atlas aims to assist researchers, clinicians, and industries in initiating or scaling up the applications of alpha-emitters. The Alpha Atlas aspires to act as a strategic guide, facilitating collaboration and driving forward the integration of these potent therapeutic agents into cancer treatment practices.

We report DGA extraction chromatography isolation of ⁵¹Mn from isotopically enriched ⁵⁴Fe. The method has been studied in semi-automated and automated realizations. The former achieves a decay corrected radiochemical yield of 78 ± 1 % (n = 3) and a separation factor of (1.0 ± 0.8) x 10⁵ (n = 3). With GE HealthCare's Solid Target Platform (STP) and FASTlab the latter, fully automated method achieves a decay corrected radiochemical yield of 87 ± 1 % (n = 3) and a separation factor of (2.7 ± 0.9) x 10⁴ (n = 3). Both setups efficiently isolate cyclotron-produced ⁵¹MnCl₂ suitable for human administration as determined by developed Chemistry, Manufacturing, and Controls (CMC) acceptance criteria, and support exploration of ⁵¹Mn as a clinical diagnostic tool.

Purpose: Preclinical studies suggest that trimebutine could be a potential treatment for glioblastoma. The aim of this study was to investigate the distribution, kinetics and tumor accumulation of [¹¹C]trimebutine.

Method: A proliferation assay and cell scratch healing assay were performed to confirm the antitumor effects of trimebutine on C6 glioma cells in-vitro. Trimebutine was subsequently labeled with ¹¹C. The distribution and kinetics of [¹¹C]trimebutine in health rats and rats with an orthotopic C6 glioma were evaluated by ex-vivo gamma counting and positron emission tomography, respectively. Blocking experiments with an excess of unlabeled trimebutine or the μ-opioid receptor ligand cyprodime were employed to determine if trimebutine exhibits saturable binding in the brain. In addition, plasma stability of the tracer was assessed.

Results: The proliferation assay and cell scratch healing assay confirmed that trimebutine has anti-tumor effects in-vitro. [¹¹C]Trimebutine with a radiochemical purity >98 % was synthesized in 15 ± 5 % radiochemical yield. In peripheral organs, the highest accumulation of the tracer was detected in excretion organs. In the brain, the highest tracer uptake was observed in the brainstem and the lowest in the hypothalamus, although differences between regions were small. PET imaging showed rapid brain uptake of [¹¹C]trimebutine, followed by a gradual washout. Administration of an intravenous dose of trimebutine (10 mg/kg) significantly decreased the uptake in all brain regions (p < 0.05), except midbrain. Likewise, administration of cyprodime (2 mg/kg) significantly reduced [¹¹C]trimebutine uptake in the brain (p < 0.01). However, uptake of [¹¹C]trimebutine in the tumor was not significantly different from its brain uptake in rats bearing an orthotopic C6 glioma. The percentage of intact [¹¹C]trimebutine at 60 min post injection was only 1.7 ± 0.6 %.

Conclusion: Trimebutine exhibits inhibitory effects on the growth and migration of glioma cells in a dose- and time-dependent manner. [¹¹C]Trimebutine was able to penetrate the blood-brain barrier in rats and tracer uptake could be significantly reduced by administration of a μ-opioid receptor antagonist. However, [¹¹C]trimebutine failed to selectively accumulate in orthotopic C6 glioma, which could be caused by low expression levels of the drug target in these tumors, or by fast metabolism of the tracer.

Purpose: Tau positron emission tomography (PET) has become an essential tool for the clinical diagnosis of neurodegenerative diseases and the study of tau pathology in the brain. However, some tau tracers exhibit off-target binding in the basal ganglia, choroid plexus, and meninges. Recently, transmembrane protein 106B (TMEM106B) was identified to form novel amyloid filaments in the brain during aging. In this study, we explored the possibility that TMEM106B aggregates might be responsible for off-target binding of tau PET tracers in the choroid plexus.

Methods: The binding properties of ¹⁸F-labeled tau and amyloid tracers against choroid plexus tissues from postmortem human brains were evaluated through in vitro autoradiography and in vitro binding assays and compared with histochemical staining.

Results: Autoradiography showed strong binding of [¹⁸F]PM-PBB3 followed by [¹⁸F]flortaucipir in the choroid plexus. Immunostaining of the same sections revealed a high level of transmembrane protein 106B aggregates, which are thioflavin-S-labeled Biondi ring structures, in the choroid plexus epithelium and co-localization with PM-PBB3-stained structures. In contrast, co-localization of flortaucipir with TMEM106B immunoreactivity was not confirmed because flortaucipir had a low fluorescence intensity. In vitro binding assays for [¹⁸F]PM-PBB3 and [¹⁸F]flortaucipir demonstrated high affinities for collagenase A-treated choroid plexus homogenate containing transmembrane protein 106B aggregates.

Conclusion: This study demonstrated high affinity of [¹⁸F]PM-PBB3 for TMEM106B aggregates in the choroid plexus. In vivo off-target binding of [¹⁸F]PM-PBB3 to the choroid plexus might result from binding to TMEM106B aggregates.