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Radiopharmaceuticals for Diagnostics
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Table 3.3 represents published PET-radiopharmaceuticals that are used in oncological patients. The main development is the emerging of tracers for PSMA ([18F]PSMA1007) to diagnose and treat prostate cancer [24]. Furthermore, tracers for EGFR-tk are developed for treatment follow-up. There is a striking explosion of using [89Zr]antibodies for many different targets. In comparison to the neurology tracers there are a few new tracers labelled with 11C or 18F published in the last 5 years. Physicians still use established tracers such as [18F]FDG, [18F]FET, [18F]FDOPA and [18F]FLT.
Prostate cancer
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Jurgen J Fütterer, Fillip Kossov, Henkjan Huisman
The most promising radiotracer class is represented by the inhibitors of the prostate-specific membrane antigen (PSMA) protein (90–92). PSMA is an enzymatic system physiologically expressed on external membrane prostate cells that can be detected at higher concentrations in prostate cancer cells (92).
Molecular Imaging of Viable Cancer Cells
Published in Shoogo Ueno, Bioimaging, 2020
In order to expand the range of target cancers, we next focused on cancer-associated carboxypeptidases. Especially, we focused on the glutamate carboxypeptidase activity of prostate-specific membrane antigen (PSMA), which is a type II transmembrane glycoprotein that is overexpressed in prostate cancer.53–55 Based on our finding that aryl glutamate conjugates with an azoformyl linker are recognized by PSMA and have a sufficiently low LUMO energy level to quench the fluorophore through photoinduced electron transfer, we established a new design strategy for activatable fluorescence probes to visualize carboxypeptidase activity, and developed a first-in-class activatable fluorescence probe for detecting the carboxypeptidase activity of PSMA (Figure 2.11).56 We confirmed that the developed probe allowed us to visualize the CP activity of PSMA in living cells and in clinical specimens from prostate cancer patients. This probe is expected to be useful for rapid intraoperative detection and diagnosis of prostate cancer.
What’s to come in PSMA therapies and diagnostics: A summary of clinical trials involving PSMA radioligand-based therapeutic and/or diagnostic approaches with active recruitment
Published in Expert Review of Anticancer Therapy, 2023
Debra Ann Dawson, Michael Lock, David Laidley, Glenn Bauman
There is much work to be done to develop optimized guidelines for the broad implementation of PSMA-based PET diagnostic imaging as well as PSMA-based RLTs, as evidenced by the narrow breadth of evidence-based applications presently available for clinical practice. It is the goal of this review to summarize the ongoing PSMA-based diagnostic and therapeutic clinical trials in order to help guide future studies and to provide a glimpse of potential upcoming applications of PSMA-targeting agents. We will discuss the full breadth of PSMA ligand-based studies currently underway in order to capture the diverse and exciting potential of the field. Broad categories of PSMA-based research include the broader applicability of PSMA-PET in diagnosing, monitoring, and tailoring care in PC; the optimal timing, dosing, and radiopharmaceutical choices in PSMA RLT treatment of PC; the relevance of PSMA-PET and PSMA-RLT in non-PC conditions; and in-development immunotherapy approaches making use of PSMA ligands. In summarizing the ongoing research in the PSMA field, we aim to identify key studies to follow which are expected to expand on the current usage of PSMA ligands, to clarify the timeline of those expected changes, and to identify gaps in the landscape of trials which may guide researchers to seek to fill those gaps. Of note, we review the existing clinical trials, but we do not review any preliminary results or require that preliminary results be available. Our conclusions and hypotheses are drawn based on study design.
Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review
Published in Expert Review of Anticancer Therapy, 2023
Kanchi Patell, Matthew Kurian, Jorge A. Garcia, Prateek Mendiratta, Pedro C. Barata, Angela Y. Jia, Daniel E. Spratt, Jason R. Brown
Fatigue, nausea, and dry mouth were the most commonly reported adverse events in patients receiving 177Lu-PSMA-617 [17]. Hematological toxicity was noted to be one of the most commonly reported adverse side effect related to 177Lu PSMA therapy and was especially seen in patients with a heavy burden of skeletal metastases and borderline marrow function [89–91]. Up to 10–25% of men had a Grade 1–2 reduction in hemoglobin or platelets [89]. Anemia, leukopenia, and thrombocytopenia were infrequently observed in some patients receiving LuPSMA therapy [48]. As a result of the physiologic uptake of this therapy in salivary glands, some patients have experienced mild and transient xerostomia as a side effect [49]. In order to reduce these adversities, many studies used ice packs thirty minutes before and up to four hours after the injection [50,89]. No changes were noticed in body temperature or blood pressure [73]. As per the REALITY study, grade 3 or 4 anemia, fatigue, thrombocytopenia, and lymphopenia were the four most common AEs related to 177Lu-PSMA-617 RLT and should be monitored closely during treatment [63].
Utilizing RNA nanotechnology to construct negatively charged and ultrasound-responsive nanodroplets for targeted delivery of siRNA
Published in Drug Delivery, 2022
Lu Guo, Dandan Shi, Mengmeng Shang, Xiao Sun, Dong Meng, Xinxin Liu, Xiaoying Zhou, Jie Li
In order to achieving specific targeting of NDs to tumor cells, one PSMA targeting ligand, RNA aptamer (A10-3.2) was conjugated to the bWJ branch of 3WJ-pRNA for displaying on the NDs surface. The expression of PSMA is associated with more aggressive diseases in prostate cancer (Nauseef et al., 2021). Many PSMA ligands have been developed, such as aptamers, engineered antibodies, and monoclonal antibodies. Among these targeted ligands, aptamers composed of nucleotides or deoxynucleotide have advantages compared with other ligands such as strong specificity, low-immunogenicity, and non-toxicity (Wu et al., 2017; Nauseef et al., 2021). As the above advantages, aptamers have been extensively applied in molecular imaging and targeted therapies. Herein, RNA aptamer A10-3.2 was conjugated to the 3WJ-pRNA nanoparticles, and then displayed on outer surface of NDs through cholesterol-mediated anchoring.