An Albumin-Binding PSMA Ligand with Higher Tumor Accumulation for PET Imaging of Prostate Cancer

Prostate-specific membrane antigen (PSMA) is an ideal target for the diagnosis and treatment of prostate cancer. Due to the short half-life in blood, small molecules/peptides are rapidly cleared by the circulatory system. Prolonging the half-life of PSMA probes has been considered as an effective strategy to improve the tumor detection. Herein, we reported a 64Cu-labeled PSMA tracer conjugating with maleimidopropionic acid (MPA), 64Cu-PSMA-CM, which showed an excellent ability to detect PSMA-overexpressing tumors in delayed time. Cell experiments in PSMA-positive 22Rv1 cells, human serum albumin binding affinity, and micro-PET imaging studies in 22Rv1 model were performed to investigate the albumin binding capacity and PSMA specificity. Comparisons with 64Cu-PSMA-BCH were performed to explore the influence of MPA on the biological properties. 64Cu-PSMA-CM could be quickly prepared within 30 min. The uptake of 64Cu-PSMA-CM in 22Rv1 cells increased over time and it could bind to HSA with a high protein binding ratio (67.8 ± 1.5%). When compared to 64Cu-PSMA-BCH, 64Cu-PSMA-CM demonstrated higher and prolonged accumulation in 22Rv1 tumors, contributing to high tumor-to-organ ratios. These results showed that 64Cu-PSMA-CM was PSMA specific with a higher tumor uptake, which demonstrated that MPA is an optional strategy for improving the radioactivity concentration in PSMA-expressing tumors and for developing the ligands for PSMA radioligand therapy

Synthesis of Rice Husk-Based MCM-41 for Removal of Aflatoxin B₁ from Peanut Oil

Edible oils, especially peanut oil, usually contain aflatoxin B1 (AFB1) at extremely high concentrations. This study focused on the synthesis of rice husk-based mesoporous silica (MCM-41) for the removal of AFB1 from peanut oil. MCM-41 was characterized by X-ray diffraction, N2 physisorption, and transmission electron microscope. MCM-41 was shown to have ordered channels with high specific surface area (1246 m2/g), pore volume (1.75 cm3/g), and pore diameter (3.11 nm). Under the optimal concentration of 1.0 mg/mL of the adsorbent dose, the adsorption behavior of MCM-41, natural montmorillonite (MONT), and commercial activated carbon (CA) for AFB1 were compared. The adsorption of AFB1 in peanut oil onto the three adsorbents was slower compared to that of AFB1 in an aqueous solution. In addition, the pseudo-second-order kinetic model better fit the adsorption kinetics of AFB1, while the adsorption mechanism followed the Langmuir adsorption isotherm on the three adsorbents. The calculated maximum adsorbed amounts of AFB1 on MONT, MCM-41, and CA were 199.41, 215.93, and 248.93 ng/mg, respectively. These results suggested that MCM-41 without modification could meet market demand and could be considered a good candidate for the removal of AFB1 from peanut oil. This study provides insights that could prove to be of economic and practical value

Construction and Preclinical Evaluation of ¹²⁴I/¹²⁵I‑Labeled Antibody Targeting T Cell Immunoglobulin and Mucin Domain‑3

T cell immunoglobulin and mucin domain-3 (TIM3; HAVCR2) is a transmembrane protein that exerts negative regulatory control over T cell responses. Studies have demonstrated an upregulation of TIM3 expression in tumor-infiltrating lymphocytes (TILs) in cancer patients. In this investigation, a series of monoclonal antibodies targeting TIM3 were produced by hybridoma technology. Among them, C23 exhibited favorable biological properties. To enable specific binding, we developed a 124I/125I-C23 radio-tracer via N-bromosuccinimide (NBS)-mediated labeling of the monoclonal antibody C23. Binding affinity and specificity were assessed using the 293T-TIM3 cell line, which overexpresses TIM3, and the parent 293T cells. Furthermore, biodistribution and in vivo imaging of 124I/125I-C23 were examined in HEK293TIM3 xenograft models and allograft models of 4T1 (mouse breast cancer cells) and CT26 (mouse colon cancer cells). Micro-PET/CT imaging was conducted at intervals of 4, 24, 48, 72, and/or 96 h post intravenous administration of 3.7–7.4 MBq 124I-C23 in the respective model mice. Additionally, immunohistochemistry (IHC) staining of TIM3 expression in dissected tumor organs was performed, along with an assessment of the corresponding expression of Programmed Death 1 (PD1), CD3, and CD8 in the tumors. The C23 monoclonal antibody (mAb) specifically binds to TIM3 protein with a dissociation constant of 23.28 nM. The 124I-C23 and 125I-C23 radio-tracer were successfully prepared with a labeling yield of 83.59 ± 0.35% and 92.35 ± 0.20%, respectively, and over 95.00% radiochemical purity. Stability results indicated that the radiochemical purity of 124I/125I-C23 in phosphate-buffered saline (PBS) and 5% human serum albumin (HSA) was still >80% after 96 h. 125I-C23 uptake in 293T-TIM3 cells was 2.80 ± 0.12%, which was significantly higher than that in 293T cells (1.08 ± 0.08%), and 125I-C23 uptake by 293T-TIM3 cells was significantly blocked at 60 and 120 min in the blocking groups. Pharmacokinetics analysis in vivo revealed an elimination time of 14.62 h and a distribution time of 0.4672 h for 125I-C23. Micro-PET/CT imaging showed that the 124I-C23 probe uptake in the 293T-TIM3 model significantly differed from that of the negative control group and blocking group. In the humanized mouse model, the 124I-C23 probe had obvious specific uptake in the 4T1 and CT26 models and maximum uptake at 24 h in tumor tissues (SUVmax (the maximum standardized uptake value) in 4T1 and CT26 humanized TIM3 murine tumor models: 0.59 ± 0.01 and 0.76 ± 0.02, respectively). Immunohistochemistry of tumor tissues from these mouse models showed comparable TIM3 expression. CD3 and CD8 cells and PD-1 expression were also observed in TIM3-expressing tumor tissues. The TIM3-targeting antibody C23 showed good affinity and specificity. The 124I/125I-C23 probe has obvious targeting specificity for TIM3 in vitro and in vivo. Our results suggest that 124I/125I-C23 is a promising tracer for TIM3 imaging and may have great potential in monitoring immune checkpoint drug efficacy