Exploring the impact of PEGylation on pharmacokinetics: a size-dependent effect of polyethylene glycol on prostate-specific membrane antigen inhibitors.

Background: Prostate cancer is the second most frequent cancer and the fifth leading cause of cancer-related deaths in men. Prostate-specific membrane antigen (PSMA) as a target has gained increasing attention. This research aims to investigate and understand how altering size of PEG impacts the in vitro and in vivo behavior and performance of PSMA inhibitors, with a specific focus on their pharmacokinetic characteristics and targeting properties.

High Affinity and FAP-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake for FAP Inhibitors.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts, making it an attractive target for both imaging and therapy of malignancy. This study presents a range of novel FAP inhibitors derived from amino derivatives of UAMC1110, incorporating polyethylene glycol and bulky groups containing bifunctional DOTA chelators. The compounds labeled with gallium-68 were developed and characterized to study biodistribution properties and tumor-targeting performance in nude mice bearing U87MG tumor xenografts.

The effects of novel macrocyclic chelates on the targeting properties of the Ga-labeled Gastrin releasing peptide receptor antagonist RM2.

Background: The gastrin-releasing peptide receptor (GRPr) is a molecular target for the visualization of prostate cancer. Bombesin (BN) analogs are short peptides with a high affinity for GRPr. RM2 is a bombesin-based antagonist.

Improve the Biodistribution with Bulky and Lipophilic Modification Strategies on Lys-Urea-Glu-Based PSMA-Targeting Radiotracers.

Since prostate-specific membrane antigen (PSMA) is upregulated in nearly all stages of prostate cancer (PCa), PSMA can be considered a viable diagnostic biomarker and treatment target in PCa. In this study, we have developed five Ga-labeled PSMA-targeted tracers, Ga-Flu-1, Ga-Flu-2, Ga-9-Ant, Ga-1-Nal, and Ga-1-Noi, to investigate the effect of lipophilic bulky groups on the pharmacokinetics of PSMA inhibitors compared to Ga-PSMA-11 and then explore their in vitro and in vivo properties. Ga-labeled PSMA inhibitors were obtained in 88.

Halogen Replacement on the Lysine Side Chain of Lys-Urea-Glu-Based PSMA Inhibitors Leads to Significant Changes in Targeting Properties.

Purpose: Investigate the impact of various halogens on pharmacokinetics, biodistribution, and micro positron emission tomography/computed tomography (PET/CT) imaging of Glu-urea-Lys-based prostate-specific membrane antigen (PSMA) inhibitors.

Procedures: Based on the modification of SC691, a small molecule inhibitor of PSMA previously developed by our group, we synthesized Ga-labeled compounds by modifying the lysine terminal amino with different halogenated phenyl substituents. After complete characterization, in vitro and in vivo properties were studied.

Cucurbitacin I induces apoptosis in ovarian cancer cells through oxidative stress and the p190B‑Rac1 signaling axis.

Ovarian cancer is a serious threat to women's life and health, with a high mortality rate. Therefore, in addition to improving surgery for ovarian cancer, it is particularly important to develop novel drug treatments. In the present study, the anticancer effects of cucurbitacin I, a natural product, were investigated.