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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).
Urology
Published in Gozie Offiah, Arnold Hill, RCSI Handbook of Clinical Surgery for Finals, 2019
Investigations➣ Serum PSA - Screening test with high sensitivity, but low specificity. It is an indication to consider prostate biopsy.➣ Transrectal ultrasound (TRUS) and biopsy with prophylactic PO ciprofloxacin +/- IV gentamicin if additional risk factors for infection such as diabetes➣ Pelvic and prostate MRI - To detect the presence of extracapsular extension➣ Isotope bone scan - to assess for bone metastases.➣ Staging CT TAP in high risk cases.PSMA PET scan
Radiopharmaceuticals for SPECT
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Prostate-specific membrane antigen (PSMA) is an integral membrane protein with an enzymatic active site in an extracellular domain. PSMA is upregulated in prostate cancer, particularly in advanced, hormone-independent and metastatic disease (239). It is also expressed in the neovasculature of nearly all solid tumors (240). Adding further to the attractiveness of PSMA as an imaging target is its limited pattern of expression, primarily within prostate, small bowel, proximal renal tubule and brain (241). Within the brain PSMA is known as glutamate carboxypeptidase II (GCPII, also known as NAAG peptidase), where it catalyzes the hydrolysis of NAAG to glutamate and N-acetylaspartate (242). PSMA/GCPII is an active target for the development of imaging agents and has recently been reviewed (243). One class of PSMA inhibitors has been designed by replacing the glutamide moiety of a PSMA substrate-like NAAG with a urea. Two urea based PSMA inhibitors DCIT and compound 28 labeled with single photon emitters that have shown high specific uptake in PSMA + mouse tumor xenografts are shown in Figure 18 (244,245).
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
PSMA, also known as folate hydrolase I or glutamate carboxypeptidase II, is a type II, 750-amino acid transmembrane protein [34,35]. Normal, benign, and malignant prostate tissue including intraepithelial neoplasia and metastatic specimens express PSMA [36]. Its function is to hydrolyze prostatic fluid peptides, generate glutamate as a cell-surface peptidase, and improve cell survival and proliferation [37,38]. PSMA levels have been expressed in healthy prostate, small intestine, proximal renal tubule, and salivary and lacrimal glands [39–41]. PSMA is overexpressed 100 to 1000 times in prostate cancer and is further increased in metastatic and castration resistant prostate cancer [37,42]. It also has been shown to be expressed in other neoplasms, such as renal cell carcinoma, hepatocellular carcinoma, and colon carcinoma [34,43,44]. There is also a direct correlation between the density of expression of PSMA on prostate cancer cells and Gleason score of prostate cancer [26]. The high PSMA expression in prostate cancer makes it an appealing target for radionucleotide therapy. However, since PSMA is not prostate-specific there is a risk of delivery of radiation to other organs. Therefore, it is important to consider the side effect profile of PSMA‐targeted therapy and understand the safest dose of radiotherapy that can be delivered to the patient without causing significant radiation damage to non‐target organs [26,45].
Utilizing clinical, pathological and radiological information to guide postoperative radiotherapy in prostate cancer
Published in Expert Review of Anticancer Therapy, 2023
Jerusha Padayachee, Simone Chaudhary, Brian Shim, Jonathan so, Remy Lim, Srinivas Raman
Over the last decade, there has been increasing utilization of molecular imaging in guiding cancer therapy through initial staging, assessment of treatment response, and identifying relapse. In the setting of prostate cancer, PET/CT using PSMA tracers radiolabelled with 68-Gallium (68Ga) or 18-Fluorine (18F) has emerged as an important imaging modality. PSMA is a transmembrane glycoprotein that is overexpressed in prostate cancer cells. In normal human prostate, PSMA is localized to the cytoplasm and apical side of the epithelium lining prostatic ducts [76]. With malignant transformation of prostate tissue, PSMA is transferred to the luminal surface of the ducts [76]. To that end, PSMA offers 100–1000 fold increase in expression of prostatic cancer cells compared with normal tissue, making it an ideal molecular imaging target [77]. In addition, PSMA is easily internalized into prostate cancer cells once bound by small radiolabelled molecules such as 68Ga-PSMA-11 and 18F-DCFPyL [78].
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.