Imaging of prostate cancer: optimizing affinity to prostate specific membrane antigen by spacer modifications in a tumor spheroid model

Krishnan, Mena Asha; Pandit, Amit; Sharma, Rajesh; Chelvam, Venkatesh

doi:10.1080/07391102.2021.1936642

Cited by 4 publications

(4 citation statements)

References 53 publications

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“…( 40 ) attempted to change the glutamine structure in the linker to a benzene structure to obtain 16 based on the structure of 15 , the probe showed slower clearance and lower affinity than 15 because of the introduction of the benzene ring structure on the linker. The same is true for the principle of designing radionuclide probes and modifications in the linker area can significantly improve the tumor uptake rate and in vivo pharmacokinetics ( 37 , 62 ).…”

Section: Near-infrared Afpismentioning

confidence: 92%

“…Prostate-specific membrane antigen (PSMA), a peripheral glutamate carboxypeptidase, is a biomarker highly expressed by prostate cancer cells. PSMA is located on the cell membrane surface, and its active site faces the outside of the cell; this enzyme has become a common target for AfPIs ( 37 ). Its representative inhibitor structure is glutamate-urea-lysine.…”

Section: Near-infrared Afpismentioning

confidence: 99%

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Affinity probes based on small-molecule inhibitors for tumor imaging

Wang

et al. 2022

Front. Oncol.

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Methods for molecular imaging of target areas, including optical imaging, radionuclide imaging, magnetic resonance imaging and other imaging technologies, are helpful for the early diagnosis and precise treatment of cancers. In addition to cancer management, small-molecule inhibitors are also used for developing cancer target probes since they act as the tight-binding ligands of overexpressed proteins in cancer cells. This review aims to summarize the structural designs of affinity probes based on small-molecule inhibitors from the aspects of the inhibitor, linker, dye and radionuclide, and discusses the influence of the modification of these structures on affinity and pharmacokinetics. We also present examples of inhibitor affinity probes in clinical applications, and these summaries will provide insights for future research and clinical translations.

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Section: Near-infrared Afpismentioning

confidence: 92%

Section: Near-infrared Afpismentioning

confidence: 99%

Affinity probes based on small-molecule inhibitors for tumor imaging

Wang

et al. 2022

Front. Oncol.

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“…For this, Venkatesh Chelvam et al designed and synthesized six PSMA-targeted fluorescent probes (rhodamine bioconjugates 12-17) with different aromatic modified linkers to investigate the effect of hydrophobic aromatic moieties in the probe design on its PSMA affinity and in vitro performance. [50] In the design, EUE was used as the PSMA targeting moiety and rhodamine B as the fluorescent moiety. Computerized molecular docking studies [51] showed that the positioning of the three aromatic moieties in the linker of rhodamine bioconjugate 12 formed three hydrophobic interactions with the amino acid residues in the PSMA tunnel, Π-cation interaction, Π-Π interactions, and Π-alkyl interaction, respectively, giving the best similarity to the cocrystalline ligand JB7 scores (0.620 vs 0.775).…”

Section: Small-molecule Inhibitor Conjugatesmentioning

confidence: 99%

Advances in Prostate‐Specific Membrane Antigen (PSMA)‐Targeted Phototheranostics of Prostate Cancer

Wang

Liu

et al. 2022

Small Structures

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With the advent of the era of precision medicine, prostate‐specific membrane antigen (PSMA)‐targeted theranostic strategies have had a profound impact on prostate cancer research. As a specific membrane antigen target, PSMA is not only widely expressed in prostate cancer tissues but its expression is also correlated with tumor aggressiveness. Because of the noninvasiveness, real‐time nature, high sensitivity, and low side effects of phototheranostics, in recent years, there has been a rapid advancement in PSMA‐targeted phototheranostics, such as near‐infrared fluorescence imaging and imaging‐guided surgical navigation, photoacoustic imaging, dual‐modality hybrid imaging and imaging‐guided surgical navigation, photodynamic therapy, and photothermal therapy. Herein, the design and application of various types of imaging probes and photosensitizers based on PSMA targeting developed in the past two decades are reviewed, with a focus on molecular design strategies for near‐infrared fluorescent probes and hybrid tracers. In addition, the challenges of and future opportunities for the clinical translation of phototheranostics in the field of prostate cancer are discussed.

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“…Basic Protocol 3 details an assay to assess the viability of the prostate cancer spheroids after 48 hr of formation. Finally, Basic Protocol 4 describes the extent of penetration and distribution of small molecule‒targeted fluorescent agents specific for a biomarker (prostate‐specific membrane antigen [PSMA]) overexpressed in LNCaP spheroids (Krishnan, Pandit, Sharma, & Chelvam, 2021; Krishnan, Yadav, Roach, & Chelvam, 2021).…”

Section: Introductionmentioning

confidence: 99%

Agarose Micro‐Well Platform for Rapid Generation of Homogenous 3D Tumor Spheroids

2021

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In recent years, 3D culture of tumor spheroids has managed to revolutionize cancer research and drug discovery. 2D monolayer cells grown in cell culture flasks undergo radical changes in cell behavior, structure, and function owing to varying environmental cues and are unable to provide predictive data for preclinical evaluation. 3D tumor spheroids can better recapitulate tumor architecture, cell-cell and cell-matrix connectivity, and the tissue complexity of tumors grown in animal models. However, many of the existing techniques to culture 3D spheroids are time-consuming and ineffective and produce irregularshaped spheroids that cannot be easily incorporated in biological assays. The set of protocols described herein makes use of a commercial hair brush as a template to create concave micro-well impressions in agarose. This technique is easy, inexpensive, and adaptable and also has the ability to produce uniform, homogenous cancer spheroids, with large diameter (∼1000 μm) and thickness (∼250 μm), within 24 to 48 hr after cell seeding. The 3D spheroids produced using the agarose micro-well platform function as an excellent 3D in vitro model for understanding the extent of penetration, uptake, and distribution of targeted cargos such as a diagnostic or therapeutic agents for identification and treatment of cancer.

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Imaging of prostate cancer: optimizing affinity to prostate specific membrane antigen by spacer modifications in a tumor spheroid model

Cited by 4 publications

References 53 publications

Affinity probes based on small-molecule inhibitors for tumor imaging

Affinity probes based on small-molecule inhibitors for tumor imaging

Advances in Prostate‐Specific Membrane Antigen (PSMA)‐Targeted Phototheranostics of Prostate Cancer

Agarose Micro‐Well Platform for Rapid Generation of Homogenous 3D Tumor Spheroids

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