Nuclear medicine and biology最新文献

Brain pretargeted nuclear imaging for the diagnosis of various neurodegenerative diseases is a quickly developing field. The tetrazine ligation is currently the most explored approach to achieve this goal due to its remarkable properties. In this work, we evaluated the performance of F-537-Tetrazine, previously developed by Biogen, and N-(3-[¹⁸F]fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine, previously developed in our group, thereby allowing for the direct comparison of these two imaging probes. The evaluation included synthesis, radiolabeling and a comparison of the physicochemical properties of the compounds. Furthermore, their performance was evaluated by in vitro and in vivo pretargeting models. This study indicated that N-(3-[¹⁸F] fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine might be more suited for brain pretargeted imaging.

Objective

Diabetic patients often experience chronic inflammation and fibrosis in their cardiac tissues, highlighting the pressing need for the development of sensitive diagnostic methods for longitudinal assessment of diabetic cardiomyopathy. This study aims to evaluate the significance of an inflammatory marker known as translocator protein (TSPO) in a positron emission tomography (PET) protocol for longitudinally monitoring cardiac dysfunction in a diabetic animal model. Additionally, we compared the commonly used radiotracer, ¹⁸F-fluoro-2-deoxy-d-glucose (¹⁸F-FDG).

Methods

Fourteen 7-week-old female Sprague-Dawley rats were used in this study. Longitudinal PET experiments were conducted using ¹⁸F-N-2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide (¹⁸F-FEPPA) (n = 3), the TSPO radiotracer, and ¹⁸F-FDG (n = 3), both before and after the onset of diabetes. Histological and immunohistochemical staining assays were also conducted in both the control (n = 4) and diabetes (n = 4) groups.

Results

Results indicated a significant increase in cardiac tissue uptake of ¹⁸F-FEPPA after the onset of diabetes (P < 0.05), aligning with elevated TSPO levels observed in diabetic animals according to histological data. Conversely, the uptake of ¹⁸F-FDG in cardiac tissue significantly decreased after the onset of diabetes (P < 0.05).

Conclusion

These findings suggest that ¹⁸F-FEPPA can function as a sensitive probe for detecting chronic inflammation and fibrosis in the cardiac tissues of diabetic animals.

Patients with HER2-positive and triple negative breast cancer (TNBC) are associated with increased risk to develop metastatic disease including reoccurring disease that is resistant to standard and targeted therapies. The α_Vβ₃ has been implicated in BC including metastatic disease. The aims of this study were to investigate the potential of α_Vβ₃-targeted peptides to deliver radioactive payloads to BC tumors expressing α_Vβ₃ on the tumor cells or limited to the tumors' neovascular. Additionally, we aimed to assess the pharmacokinetic profile of the targeted α-particle therapy (TAT) agent [²²⁵Ac]Ac-DOTA-cRGDfK dimer peptide and the in vivo generated decay daughters. The expression of α_Vβ₃ in a HER2-positive and a TNBC cell line were evaluated using western blot analysis. The pharmacokinetics of [¹¹¹In]In-DOTA-cRGDfK dimer, a surrogate for the TAT-agent, was evaluated in subcutaneous mouse tumor models. The pharmacokinetic of the TAT-agent [²²⁵Ac]Ac-DOTA-cRGDfK dimer and its decay daughters were evaluated in healthy mice. Selective uptake of [¹¹¹In]In-DOTA-cRGDfK dimer was shown in subcutaneous tumor models using α_Vβ₃-positive tumor cells as well as α_Vβ₃-negative tumor cells where the expression is limited to the neovasculature. Pharmacokinetic studies demonstrated rapid accumulation in the tumors with clearance from non-target organs. Dosimetric analysis of [²²⁵Ac]Ac-DOTA-cRGDfK dimer showed the highest radiation absorbed dose to the kidneys, which included the contributions from the free in vivo generated decay daughters. This study shows the potential of delivering radioactive payloads to BC tumors that have α_Vβ₃ expression on the tumor cells as well as limited expression to the neovascular of the tumor. Furthermore, this work determines the radiation absorbed doses to normal organs/tissues and identified key organs that act as suppliers and receivers of the actinium-225 free in vivo generated α-particle-emitting decay daughters.

This report describes an updated, fully automated method for the production of [¹¹C]PIB on a cassette-based automated synthesis module. The method allows for two separate productions of [¹¹C]PIB, both of which meet all specification for use in clinical studies. The GE FASTlab developer system was used to create the cassette design as well as the controlling tracer package. The method takes 16 min from the delivery of [¹¹C]MeOTf to the FASTlab, or 35 min from the End of Bombardment; and reliably produces 3547 ± 586 MBq of [¹¹C]PIB in high radiochemical purity (> 98 %). This methodology increases the production capacity of radiopharmaceutical facilities for [¹¹C]PIB, and can easily produce 4 batches in a single day with limited infrastructure footprint.

Introduction

Due to its decay and chemical properties, interest in manganese-52 has increased for development of long-lived PET radiopharmaceuticals. Its long half-life of 5.6 days, low average positron energy (242 keV), and sufficient positron decay branching ratio make it suitable for radiolabeling macromolecules for investigating slow biological processes. This work aims to establish suitable chelators for manganese-52 that can be radiolabeled at mild conditions through the evaluation of commercially available chelators.

Methods

Manganese-52 was produced through the nuclear reaction ^NatCr(p,n)⁵²Mn by irradiation of natural chromium targets on a TR24 cyclotron followed by purification through ion exchange chromatography. The radiolabeling efficiencies of chelators: DOTA, DiAmsar, TETA, DO3A, NOTA, 4′-Formylbenzo-15-crown-5, Oxo-DO3A, and DFO, were assessed by investigating the impact of pH, buffer type, and temperature. In vitro stability of [⁵²Mn]Mn(DO3A)⁻, [⁵²Mn]Mn(Oxo-DO3A)⁻, and [⁵²Mn]Mn(DOTA)²⁻ were evaluated in mouse serum. The radiocomplexes were also evaluated in vivo in mice. Crystals of [Mn(Oxo-DO3A)]⁻ were synthesized by reacting Oxo-DO3A with MnCl₂ and characterized by single crystal X-ray diffraction.

Results

Yields of 185 ± 19 MBq (5.0 ± 0.5 mCi) (n = 4) of manganese-52 were produced at the end of a 4 h, 15 μA, bombardment with 12.5 MeV protons. NOTA, DO3A, DOTA, and Oxo-DO3A chelators were readily radiolabeled with >96 % radiochemical purity at all conditions. Manganese radiocomplexes of Oxo-DO3A, DOTA, and DO3A remained stable in vitro up to 5 days and exhibited different biodistribution profiles compared to [⁵²Mn]MnCl₂. The solid-state structure of Mn-Oxo-DO3A complex was determined by single-crystal X-ray diffraction.

Conclusions

DO3A and Oxo-DO3A are suitable chelators for manganese-52 which are readily radiolabeled at mild conditions with high molar activity, and demonstrate both in vitro and in vivo stability.