In vitro and in vivo comparative study of a novel 68Ga-labeled PSMA-targeted inhibitor and 68Ga-PSMA-11. 2021

Huanyu Chen, and Ping Cai, and Yue Feng, and Zhanliang Sun, and Yinwen Wang, and Yue Chen, and Wei Zhang, and Nan Liu, and Zhijun Zhou
The Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Jiangyang District, Luzhou, Sichuan, China.

68Ga-radiolabeled small molecules that specifically target prostate-specific membrane antigen (PSMA) have been extensively investigated, and some of these tracers have been used in the diagnosis of prostate cancer via 68Ga-positron emission tomography (68Ga-PET). Nevertheless, current 68Ga-labeled radiotracers show only fair detection rates for metastatic prostate cancer lesions, especially those with lower levels of prostate specific antigen (PSA), which often occurs in the biochemical recurrence of prostate cancer. The goal of this study was to design and synthesize a new PSMA-targeted radiotracer, 68Ga-SC691, with high affinity for prostate cancer cells and excellent pharmacokinetics. To this end, structural optimization was carried out on the bifunctional group, target motif, and linker while the high affinity targeting scaffold remained. To explore its potential in the clinic, a comparative study was further performed in vitro and in vivo between 68Ga-SC691 and 68Ga-PSMA-11, a clinically approved tracer for PSMA-positive prostate cancer. SC691 was radiolabeled to provide 68Ga-SC691 in 99% radiolabeling yield under mild conditions. High uptake and a high internalization ratio into LNCaP cells were observed in in vitro studies. In vivo studies showed that 68Ga-SC691 had favorable biodistribution properties and could specifically accumulate on PSMA-positive LNCaP xenografts visualized by micro-PET/CT. This radiotracer showed excellent PET imaging quality and comparable, if not higher, uptake in LNCaP xenografts than 68Ga-PSMA-11.

UI MeSH Term Description Entries
D008297 Male Males
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D005709 Gallium Isotopes Stable gallium atoms that have the same atomic number as the element gallium, but differ in atomic weight. Ga-71 is a stable gallium isotope. Isotopes, Gallium
D005710 Gallium Radioisotopes Unstable isotopes of gallium that decay or disintegrate emitting radiation. Ga atoms with atomic weights 63-68, 70 and 72-76 are radioactive gallium isotopes. Radioisotopes, Gallium
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072078 Positron Emission Tomography Computed Tomography An imaging technique that combines a POSITRON-EMISSION TOMOGRAPHY (PET) scanner and a CT X RAY scanner. This establishes a precise anatomic localization in the same session. CT PET,CT PET Scan,PET CT Scan,PET-CT,PET-CT Scan,Positron Emission Tomography-Computed Tomography,CT PET Scans,CT Scan, PET,CT Scans, PET,PET CT Scans,PET Scan, CT,PET Scans, CT,PET-CT Scans,Scan, CT PET,Scan, PET CT,Scan, PET-CT,Scans, CT PET,Scans, PET CT,Scans, PET-CT
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000954 Antigens, Surface Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated. Cell Surface Antigens,Surface Antigens,Surface Markers, Immunological,Cell Surface Antigen,Immunologic Surface Markers,Markers, Immunological Surface,Surface Antigen,Surface Markers, Immunologic,Antigen, Cell Surface,Antigen, Surface,Antigens, Cell Surface,Immunological Surface Markers,Markers, Immunologic Surface,Surface Antigen, Cell,Surface Antigens, Cell
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

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