Journal of labelled compounds & radiopharmaceuticals最新文献

Deuterium-labeled pyocyanin was prepared from deuterium-labeled phenazine methosulfate in gram scale by a simplified flow photosynthesis in water. The main product was the protonated red form of pyocyanin-d₃ (Pyo-d₃-H⁺) in 85 % yield. Quantum chemical calculations of NMR support that nitrogen-10 is protonated. The by-products of the photolysis and the stability of the photolysis mixture were carefully characterized by LC-MS and NMR. Four by-products were identified: An isomer of pyocyanin-d₃ (9%), 8-hydroxypyocyanin-d₃ (4%), 1-hydroxyphenazine (0.4%), and phenazine (1%). The Pyo-d₃-H⁺ product was stable in the photolysis solution after storage at 8°C for 2.5 years. Pure blue pyocyanin-d₃ powder was isolated from the red photolysis solution by the Surrey method in 94 % yield. The addition of the red photolysis solution of Pyo-d₃-H⁺ (100 μM) and commercial pyocyanin (100 μM) to Pseudomonas aeruginosa cultures showed the same growth curves demonstrating that the minor impurities in the photolysis solution do not affect the growth behavior of the bacteria. The protonated deuterium-labeled pyocyanin may be used directly in biological experiments, which make the methodology extremely simple and useful for biologists.

Immune checkpoint therapy has emerged as an effective treatment option for various types of cancers. Key immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and lymphocyte activation gene 3 (LAG-3), have become pivotal targets in cancer immunotherapy. Antibodies designed to inhibit these molecules have demonstrated significant clinical efficacy. Nevertheless, the ability to monitor changes in the immune status of tumors and predict treatment response remains limited. Conventional methods, such as assessing lymphocytes in peripheral blood or conducting tumor biopsies, are inadequate for providing real-time, spatial information about T-cell distributions within heterogeneous tumors. Positron emission tomography (PET) using T-cell specific probes represents a promising and noninvasive approach to monitor both systemic and intratumoral immune changes during treatment. This technique holds substantial clinical significance and potential utility. In this paper, we review the applications of PET probes that target immune cells in molecular imaging.

Programmed death-ligand 1 (PD-L1) expression is related to the efficacy and prognosis in triple-negative breast cancer. This study employed an indirect labeling method to synthesize [¹²⁵I]PI-Atezolizumab. The in vitro stability of [¹²⁵I]PI-Atezolizumab was assessed through incubation in phosphate buffered saline and fetal bovine serum, revealing sustained stability. Specific binding of [¹²⁵I]PI-Atezolizumab to MDA-MB-231 cells expressing humanized PD-L1 was assessed through in vitro incubation, yielding a K_d value comparable to that of Atezolizumab. This suggests that the labeling process did not compromise the affinity of the Atezolizumab to PD-L1. Subsequently, pharmacokinetic studies were conducted in normal mice and biodistribution experiments in tumor-bearing mice. A comparison of the biodistribution results between [¹²⁵I]PI-Atezolizumab and ¹²⁵I-labeled Atezolizumab indicated better in vivo stability for the former. Single photon emission computed tomography (SPECT)/CT imaging further confirmed the targeted specificity of [¹²⁵I]PI-Atezolizumab for PD-L1 in MDA-MB-231 xenografts, which were validated by immunohistochemistry staining. This research underscores the utility of [¹²⁵I]PI-Atezolizumab, prepared via indirect labeling, for monitoring PD-L1 in triple-negative breast cancer models.

Radioimmunoconjugates (RICs) composed of tumor-targeting monoclonal antibodies and radionuclides have been developed for diagnostic and therapeutic application. A new radiolabeling method using microfluidic devices is expected to facilitate simpler and more rapid synthesis of RICs. In the microfluidic method, microfluidic chips can promote the reaction between reactants by mixing them efficiently, and pumping systems enable automated synthesis. In this study, we synthesized RICs by the pre-labeling method, in which the radiometal is coordinated to the chelator and then the radiolabeled chelator is incorporated into the antibodies, using microfluidic devices for the first time. As a result of examining the reaction parameters including the material of mixing units, reaction temperature, and flow rate, RICs with radiochemical purity (RCP) exceeding 90% were obtained. These high-purity RICs were successfully synthesized without any purification simply by pumping three solutions of a chelating agent, radiometal, and antibody into microfluidic devices. Under the same conditions, the RCP of RICs labeled by conventional methods was below 50%. These findings indicate the utility of microfluidic devices for automatic and rapid synthesis of high-quality RICs.

Recently, the folate receptor (FR) has become an exciting target for the diagnosis of FR-positive malignancies. Nevertheless, suboptimal in vivo pharmacokinetic properties, particularly high uptake in the renal and hepatobiliary systems, are important limiting factors for the clinical translation of most FR-based radiotracers. In this study, we developed a novel ¹⁸F-labeled FR-targeted positron emission tomography (PET) tracer [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate modified with a hydrophilic linker (−Asp₂-PEG₂) to optimize its pharmacokinetic properties and conducted a comprehensive preclinical assessment. The [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate was manually synthesized within 30 min with a non-decay-corrected radiochemical yield of 16.3 ± 2.0% (n = 5). Among KB cells, [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate exhibited high specificity and affinity for FR. PET/CT imaging and biodistribution experiments in KB tumor-bearing mice showed decent tumor uptake (1.7 ± 0.3% ID/g) and significantly decreased uptake in kidneys and liver (22.2 ± 2.1 and 0.3 ± 0.1% ID/g at 60 min p.i., respectively) of [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate, compared to the known tracer [¹⁸F]AlF-NOTA-Folate (78.6 ± 5.1 and 5.3 ± 0.5 % ID/g at 90 min p.i., respectively). The favorable properties of [¹⁸F]AlF-NOTA-Asp₂-PEG₂-Folate, including its efficient synthesis, decent tumor uptake, relatively low renal uptake, and rapid clearance from most normal organs, portray it as a promising PET tracer for FR-positive tumors.