Organic determinants of PSMA expression, regulation and heterogeneity in prostate most cancers


  • Chen, C. D. et al. Molecular determinants of resistance to antiandrogen remedy. Nat. Med. 10, 33–39 (2004).

    Article 
    PubMed 

    Google Scholar
     

  • Polkinghorn, W. R. et al. Androgen receptor signaling regulates DNA restore in prostate cancers. Most cancers Discov. 3, 1245–1253 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chang, Ok.-H. et al. Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate most cancers. Proc. Natl Acad. Sci. USA 108, 13728–13733 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Grasso, C. S. et al. The mutational panorama of deadly castration-resistant prostate most cancers. Nature 487, 239–243 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Scher, H. I. et al. Elevated survival with enzalutamide in prostate most cancers after chemotherapy. N. Engl. J. Med. 367, 1187–1197 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chang, Ok.-H. et al. A gain-of-function mutation in DHT synthesis in castration-resistant prostate most cancers. Cell 154, 1074–1084 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hussain, M. et al. Enzalutamide in males with nonmetastatic, castration-resistant prostate most cancers. N. Engl. J. Med. 378, 2465–2474 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, I. D. et al. Enzalutamide with normal first-line remedy in metastatic prostate most cancers. N. Engl. J. Med. 381, 121–131 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate most cancers. Nat. Med. 22, 298–305 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Beltran, H. et al. Molecular characterization of neuroendocrine prostate most cancers and identification of latest drug targets. Most cancers Discov. 1, 487–495 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Aggarwal, R. et al. Scientific and genomic characterization of treatment-emergent small-cell neuroendocrine prostate most cancers: a multi-institutional potential examine. J. Clin. Oncol. 36, 2492–2503 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dardenne, E. et al. N-Myc induces an EZH2-mediated transcriptional program driving neuroendocrine prostate most cancers. Most cancers Cell 30, 563–577 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bluemn, E. G. et al. Androgen receptor pathway-independent prostate most cancers is sustained by FGF signaling. Most cancers Cell 32, 474–489.e476 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yamada, Y. & Beltran, H. Scientific and organic options of neuroendocrine prostate most cancers. Curr. Oncol. Rep. 23, 15 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hofman, M. S. et al. Prostate-specific membrane antigen PET-CT in sufferers with high-risk prostate most cancers earlier than curative-intent surgical procedure or radiotherapy (proPSMA): a potential, randomised, multicentre examine. Lancet 395, 1208–1216 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hofman, M. S. et al. [177Lu]-PSMA-617 radionuclide therapy in sufferers with metastatic castration-resistant prostate most cancers (LuPSMA trial): a single-centre, single-arm, part 2 examine. Lancet Oncol. 19, 825–833 (2018).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hofman, M. S. et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in sufferers with metastatic castration-resistant prostate most cancers (TheraP): a randomised, open-label, part 2 trial. Lancet 397, 797–804 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sartor, O. et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate most cancers. N. Engl. J. Med. 385, 1091–1103 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buteau, J. P. et al. PSMA and FDG-PET as predictive and prognostic biomarkers in sufferers given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate most cancers (TheraP): a biomarker evaluation from a randomised, open-label, part 2 trial. Lancet Oncol. 23, 1389–1397 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chow, Ok. M. et al. Head-to-head comparability of the diagnostic accuracy of prostate-specific membrane antigen positron emission tomography and traditional imaging modalities for preliminary staging of intermediate- to high-risk prostate most cancers: a scientific assessment and meta-analysis. Eur. Urol. 84, 36–48 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Pienta, Ok. J. et al. A part 2/3 potential multicenter examine of the diagnostic accuracy of prostate particular membrane antigen PET/CT with 18F-DCFPyL in prostate most cancers sufferers (OSPREY). J. Urol. 206, 52–61 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Perera, M. et al. Gallium-68 prostate-specific membrane antigen positron emission tomography in superior prostate cancer-updated diagnostic utility, sensitivity, specificity, and distribution of prostate-specific membrane antigen-avid lesions: a scientific assessment and meta-analysis. Eur. Urol. 77, 403–417 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Maurer, T., Eiber, M., Schwaiger, M. & Gschwend, J. E. Present use of PSMA–PET in prostate most cancers administration. Nat. Rev. Urol. 13, 226–235 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sartor, O. et al. LBA13 part III trial of [177Lu]Lu-PSMA-617 in taxane-naive sufferers with metastatic castration-resistant prostate most cancers (PSMAfore). Ann. Oncol. 34, S1324–S1325 (2023).

    Article 

    Google Scholar
     

  • Bakht, M. Ok. et al. Neuroendocrine differentiation of prostate most cancers results in PSMA suppression. Endocr. Relat. Most cancers 26, 131–146 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Bakht, M. Ok. et al. Differential expression of glucose transporters and hexokinases in prostate most cancers with a neuroendocrine gene signature: a mechanistic perspective for 18F-FDG imaging of PSMA-suppressed tumors. J. Nucl. Med. 61, 904–910 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bakht, M. Ok. et al. Panorama of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate most cancers. Nat. Most cancers 4, 699–715 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sayar, E. et al. Reversible epigenetic alterations mediate PSMA expression heterogeneity in superior metastatic prostate most cancers. JCI Perception 8, e162907 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Robinson, D. et al. Integrative medical genomics of superior prostate most cancers. Cell 161, 1215–1228 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pritchard, C. C. et al. Inherited DNA-repair gene mutations in males with metastatic prostate most cancers. N. Engl. J. Med. 375, 443–453 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Silver, D. A., Pellicer, I., Honest, W. R., Heston, W. D. & Cordon-Cardo, C. Prostate-specific membrane antigen expression in regular and malignant human tissues. Clin. Most cancers Res. 3, 81–85 (1997).

    CAS 
    PubMed 

    Google Scholar
     

  • Wright, G. L., Haley, C., Beckett, M. L. & Schellhammer, P. F. Expression of prostate-specific membrane antigen in regular, benign, and malignant prostate tissues. Urol. Oncol. 1, 18–28 (1995).

    Article 
    PubMed 

    Google Scholar
     

  • Rahn, Ok. A., Slusher, B. S. & Kaplin, A. I. Glutamate in CNS neurodegeneration and cognition and its regulation by GCPII inhibition. Curr. Med. Chem. 19, 1335–1345 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rahn, Ok. A. et al. Inhibition of glutamate carboxypeptidase II (GCPII) exercise as a therapy for cognitive impairment in a number of sclerosis. Proc. Natl Acad. Sci. USA 109, 20101–20106 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Davis, M. I., Bennett, M. J., Thomas, L. M. & Bjorkman, P. J. Crystal construction of prostate-specific membrane antigen, a tumor marker and peptidase. Proc. Natl Acad. Sci. USA 102, 5981–5986 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schülke, N. et al. The homodimer of prostate-specific membrane antigen is a practical goal for most cancers remedy. Proc. Natl Acad. Sci. USA 100, 12590–12595 (2003).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rawlings, N. D. & Barrett, A. J. Construction of membrane glutamate carboxypeptidase. Biochim. Biophys. Acta 1339, 247–252 (1997).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bernstein, L. H., Gutstein, S., Weiner, S. & Efron, G. The absorption and malabsorption of folic acid and its polyglutamates. Am. J. Med. 48, 570–579 (1970).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhao, R., Diop-Bove, N., Visentin, M. & Goldman, I. D. Mechanisms of membrane transport of folates into cells and throughout epithelia. Annu. Rev. Nutr. 31, 177–201 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Figueiredo, J. C. et al. Folic acid and danger of prostate most cancers: outcomes from a randomized medical trial. J. Natl Most cancers Inst. 101, 432–435 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sanderson, S. M., Gao, X., Dai, Z. & Locasale, J. W. Methionine metabolism in well being and most cancers: a nexus of weight loss plan and precision drugs. Nat. Rev. Most cancers 19, 625–637 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yao, V. & Bacich, D. J. Prostate particular membrane antigen (PSMA) expression provides prostate most cancers cells a progress benefit in a physiologically related folate atmosphere in vitro. Prostate 66, 867–875 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Reina-Campos, M. et al. Elevated serine and one-carbon pathway metabolism by PKCλ/ι deficiency promotes neuroendocrine prostate most cancers. Most cancers Cell 35, 385–400.e389 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaittanis, C. et al. Prostate-specific membrane antigen cleavage of vitamin B9 stimulates oncogenic signaling by metabotropic glutamate receptors. J. Exp. Med. 215, 159–175 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Palamiuc, L. & Emerling, B. M. PSMA brings new flavors to PI3K signaling: a job for glutamate in prostate most cancers. J. Exp. Med. 215, 17–19 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bakht, M. Ok. et al. Identification of other protein targets of glutamate-ureido-lysine related to PSMA tracer uptake in prostate most cancers cells. Proc. Natl Acad. Sci. USA 119, e2025710119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Uhlén, M. et al. Proteomics. Tissue-based map of the human proteome. Science 347, 1260419 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Barron, D. A. & Rowley, D. R. The reactive stroma microenvironment and prostate most cancers development. Endocr. Relat. Most cancers 19, R187–R204 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Karthaus, W. R. et al. Regenerative potential of prostate luminal cells revealed by single-cell evaluation. Science 368, 497–505 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chang, S. S. et al. Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin. Most cancers Res. 5, 2674–2681 (1999).

    CAS 
    PubMed 

    Google Scholar
     

  • Conway, R. E. et al. Prostate-specific membrane antigen (PSMA)-mediated laminin proteolysis generates a pro-angiogenic peptide. Angiogenesis 19, 487–500 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pandit-Taskar, N. et al. Indium 111-labeled J591 anti-PSMA antibody for vascular focused imaging in progressive stable tumors. EJNMMI Res. 5, 13 (2015).

    Article 

    Google Scholar
     

  • Tagawa, S. T. et al. Section 1/2 examine of fractionated dose lutetium-177-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 (177Lu-J591) for metastatic castration-resistant prostate most cancers. Most cancers 125, 2561–2569 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ruggiero, A. et al. Focusing on the interior epitope of prostate-specific membrane antigen with 89Zr-7E11 immuno-PET. J. Nucl. Med. 52, 1608–1615 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Eder, M. et al. 68Ga-complex lipophilicity and the concentrating on property of a urea-based PSMA inhibitor for PET imaging. Bioconjug. Chem. 23, 688–697 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ganguly, T. et al. A high-affinity [18F]-labeled phosphoramidate peptidomimetic PSMA-targeted inhibitor for PET imaging of prostate most cancers. Nucl. Med. Biol. 42, 780–787 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rowe, S. P. et al. Potential analysis of PSMA-targeted 18F-DCFPyL PET/CT in males with biochemical failure after radical prostatectomy for prostate most cancers. J. Nucl. Med. 61, 58–61 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kuten, J. et al. Head-to-head comparability of 68Ga-PSMA-11 with 18F-PSMA-1007 PET/CT in staging prostate most cancers utilizing histopathology and immunohistochemical evaluation as reference-standard. J. Nucl. Med. 61, 527–532 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cardinale, J. et al. Procedures for the GMP-compliant manufacturing and high quality management of [18F]PSMA-1007: a subsequent era radiofluorinated tracer for the detection of prostate most cancers. Prescription drugs 10, 77 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Youn, S. et al. Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: synthesis and structural characterization. Bioorg. Med. Chem. Lett. 25, 5232–5236 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Pavlicek, J., Ptacek, J. & Barinka, C. Glutamate carboxypeptidase II: an summary of structural research and their significance for structure-based drug design and deciphering the response mechanism of the enzyme. Curr. Med. Chem. 19, 1300–1309 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Machulkin, A. E. et al. Small-molecule PSMA ligands. Present state, SAR and views. J. Drug. Goal. 24, 679–693 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Barinka, C. et al. Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization. J. Med. Chem. 51, 7737–7743 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wu, L. Y. et al. The molecular pruning of a phosphoramidate peptidomimetic inhibitor of prostate-specific membrane antigen. Bioorg. Med. Chem. 15, 7434–7443 (2007).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Novakova, Z. et al. Unprecedented binding mode of hydroxamate-based inhibitors of glutamate carboxypeptidase II: structural characterization and organic exercise. J. Med. Chem. 59, 4539–4550 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lucaroni, L. et al. Cross-reactivity to glutamate carboxypeptidase III causes undesired salivary gland and kidney uptake of PSMA-targeted small-molecule radionuclide therapeutics. Eur. J. Nucl. Med. Mol. Imaging 50, 957–961 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bidkar, A. P. et al. Therapy of prostate most cancers with CD46-targeted 225Ac alpha particle radioimmunotherapy. Clin. Most cancers Res. 29, 1916–1928 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, Z., Heston, W. D., Wang, X. & Basilion, J. P. GCP III will not be the “off-target” for urea-based PSMA ligands. Eur. J. Nucl. Med. Mol. Imaging 50, 2944–2946 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heynickx, N., Segers, C., Coolkens, A., Baatout, S. & Vermeulen, Ok. Characterization of non-specific uptake and retention mechanisms of [177Lu]Lu-PSMA-617 within the salivary glands. Prescription drugs 16, 692 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Heynickx, N., Herrmann, Ok., Vermeulen, Ok., Baatout, S. & Aerts, A. The salivary glands as a dose limiting organ of PSMA-targeted radionuclide remedy: a assessment of the teachings learnt up to now. Nucl. Med. Biol. 98, 30–39 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Emmett, L. et al. The PRIMARY rating: utilizing intraprostatic 68Ga-PSMA PET/CT patterns to optimize prostate most cancers prognosis. J. Nucl. Med. 63, 1644–1650 (2022).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wolff, A. C. et al. Suggestions for human epidermal progress issue receptor 2 testing in breast most cancers: American Society of Scientific Oncology/School of American Pathologists medical apply guideline replace. J. Clin. Oncol. 31, 3997–4013 (2013).

    Article 
    PubMed 

    Google Scholar
     

  • Paschalis, A. et al. Prostate-specific membrane antigen heterogeneity and DNA restore defects in prostate most cancers. Eur. Urol. 76, 469–478 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kuo, P. H., Benson, T., Messmann, R. & Groaning, M. Why we did what we did: PSMA PET/CT choice standards for the VISION trial. J. Nucl. Med. 63, 816–818 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Seifert, R. et al. Second model of the prostate most cancers molecular imaging standardized analysis framework together with response analysis for medical trials (PROMISE V2). Eur. Urol. 83, 405–412 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Eiber, M. et al. Prostate most cancers molecular imaging standardized analysis (PROMISE): proposed miTNM classification for the interpretation of PSMA-ligand PET/CT. J. Nucl. Med. 59, 469–478 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Saha, G. B. Physics and Radiobiology of Nuclear Drugs (Springer Science & Enterprise Media, 2012).

  • Calais, J. et al. Security of PSMA-targeted molecular radioligand remedy with 177Lu-PSMA-617: outcomes from the potential multicenter part 2 trial RESIST-PC (NCT03042312). J. Nucl. Med. 62, 1447–1456 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Arnfield, E. G. et al. Scientific insignificance of [18F]PSMA-1007 avid non-specific bone lesions: a retrospective analysis. Eur. J. Nucl. Med. Mol. Imaging 48, 4495–4507 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, M. Y. et al. Solitary rib lesions displaying prostate-specific membrane antigen (PSMA) uptake in pre-treatment staging 68Ga-PSMA-11 positron emission tomography scans for males with prostate most cancers: benign or malignant? BJU Int. 126, 396–401 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Le Wen, C. et al. Components predicting metastatic illness in 68Ga-PSMA-11 PET-positive osseous lesions in prostate most cancers. J. Nucl. Med. 61, 1779 (2020).

    Article 

    Google Scholar
     

  • Tim, E. P. et al. Predicting outcomes of indeterminate bone lesions on 18F-DCFPyL PSMA PET/CT scans within the setting of high-risk major or recurrent prostate most cancers. J. Nucl. Med. 64, 395 (2023).

    Article 

    Google Scholar
     

  • Guner, L. A. et al. Enhancing PSMA PET/CT imaging of prostate most cancers: investigating the affect of a number of time level analysis, diuretic administration, cribriform sample, and intraductal carcinoma. Ann. Nucl. Med. 37, 618–628 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Present, Ok. et al. Investigating PSMA-targeted radioligand remedy efficacy as a operate of mobile PSMA ranges and intratumoral PSMA heterogeneity. Clin. Most cancers Res. 26, 2946–2955 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gafita, A. et al. Nomograms to foretell outcomes after 177Lu-PSMA remedy in males with metastatic castration-resistant prostate most cancers: a world, multicentre, retrospective examine. Lancet Oncol. 22, 1115–1125 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Thang, S. P. et al. Poor outcomes for sufferers with metastatic castration-resistant prostate most cancers with low prostate-specific membrane antigen (PSMA) expression deemed ineligible for 177Lu-labelled PSMA radioligand remedy. Eur. Urol. Oncol. 2, 670–676 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Violet, J. et al. Lengthy-term follow-up and outcomes of retreatment in an expanded 50-patient single-center part II potential trial of 177Lu-PSMA-617 theranostics in metastatic castration-resistant prostate most cancers. J. Nucl. Med. 61, 857–865 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alizadeh, A. A. et al. Towards understanding and exploiting tumor heterogeneity. Nat. Med. 21, 846–853 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bedard, P. L., Hansen, A. R., Ratain, M. J. & Siu, L. L. Tumour heterogeneity within the clinic. Nature 501, 355–364 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Henry, G. H. et al. A mobile anatomy of the conventional grownup human prostate and prostatic urethra. Cell Rep. 25, 3530–3542.e5 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stylianou, N. et al. A molecular portrait of epithelial-mesenchymal plasticity in prostate most cancers related to medical consequence. Oncogene 38, 913–934 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Lin, D. et al. Excessive constancy patient-derived xenografts for accelerating prostate most cancers discovery and drug growth. Most cancers Res. 74, 1272–1283 (2014).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Staniszewska, M. et al. Enzalutamide enhances PSMA expression of PSMA-low prostate most cancers. Int. J. Mol. Sci. 22, 7431 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bakht, M. Ok. et al. Affect of androgen deprivation remedy on the uptake of PSMA-targeted brokers: rising alternatives and challenges. Nucl. Med. Mol. Imaging 51, 202–211 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Meller, B. et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate most cancers cells as a goal for diagnostics and remedy. EJNMMI Res. 5, 66 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Evans, M. J. et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc. Natl Acad. Sci. USA 108, 9578–9582 (2011).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kashyap, A. et al. Quantification of tumor heterogeneity: from knowledge acquisition to metric era. Developments Biotechnol. 40, 647–676 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Assadi, M. et al. Predictive and prognostic potential of pretreatment 68Ga-PSMA PET tumor heterogeneity index in sufferers with metastatic castration-resistant prostate most cancers handled with 177Lu-PSMA. Entrance. Oncol. 12, 1066926 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lückerath, Ok. et al. Detection threshold and reproducibility of 68Ga-PSMA11 PET/CT in a mouse mannequin of prostate most cancers. J. Nucl. Med. 59, 1392–1397 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nguyen, H. M. et al. LuCaP prostate most cancers patient-derived xenografts mirror the molecular heterogeneity of superior illness and function fashions for evaluating most cancers therapeutics. Prostate 77, 654–671 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nyquist, M. D. et al. Mixed TP53 and RB1 loss promotes prostate most cancers resistance to a spectrum of therapeutics and confers vulnerability to replication stress. Cell Rep. 31, 107669 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, J. Ok. et al. Systemic surfaceome profiling identifies goal antigens for immune-based remedy in subtypes of superior prostate most cancers. Proc. Natl Acad. Sci. USA 115, E4473–E4482 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Olivier, P. et al. Section III examine of 18F-PSMA-1007 versus 18F-fluorocholine PET/CT for localization of prostate most cancers biochemical recurrence: a potential, randomized, crossover multicenter examine. J. Nucl. Med. 64, 579–585 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Morgan, R., Wermuth, D., Molina, E. & Perraillon, M. Utilization and price of radium-223 dichloride (Xofigo®) for therapy of metastatic castration-resistant prostate most cancers (mCRPR) within the U.S. Medicare inhabitants. J. Nucl. Med. 62, 1309–1309 (2021).


    Google Scholar
     

  • Hoving, H. et al. Early 18F-FDHT PET/CT as a predictor of therapy response in mCRPC handled with enzalutamide. J. Clin. Oncol. 37, 232–232 (2019).

    Article 

    Google Scholar
     

  • Puca, L. et al. Delta-like protein 3 expression and therapeutic concentrating on in neuroendocrine prostate most cancers. Sci. Transl. Med. 11, eaav0891 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • O’Donoghue, J. A. et al. Pharmacokinetics and biodistribution of a [89Zr]Zr-DFO-MSTP2109A anti-STEAP1 antibody in metastatic castration-resistant prostate most cancers sufferers. Mol. Pharm. 16, 3083–3090 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bhatia, V. et al. Focusing on superior prostate most cancers with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy. Nat. Commun. 14, 2041 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kesch, C. et al. Excessive fibroblast-activation-protein expression in castration-resistant prostate most cancers helps using FAPI-molecular theranostics. Eur. J. Nucl. Med. Mol. Imaging 49, 385–389 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • O’Keefe, D. S. et al. Mapping, genomic group and promoter evaluation of the human prostate-specific membrane antigen gene. Biochim. Biophys. Acta 1443, 113–127 (1998).

    Article 
    PubMed 

    Google Scholar
     

  • Afshar-Oromieh, A. et al. Influence of long-term androgen deprivation remedy on PSMA ligand PET/CT in sufferers with castration-sensitive prostate most cancers. Eur. J. Nucl. Med. Mol. Imaging 45, 2045–2054 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Unterrainer, L. et al. Early adjustments of PSMA PET sign after initiation of androgen receptor signaling inhibitors in mCRPC: a world multicenter retrospective examine. J. Clin. Oncol. 41, 5063–5063 (2023).

    Article 

    Google Scholar
     

  • Tagawa, S. T. et al. PSMAddition: a part 3 trial to match therapy with 177Lu-PSMA-617 plus normal of care (SoC) and SoC alone in sufferers with metastatic hormone-sensitive prostate most cancers. J. Clin. Oncol. 41, TPS5116–TPS5116 (2023).

    Article 

    Google Scholar
     

  • Emmett, L. et al. [177Lu]Lu-PSMA-617 plus enzalutamide in sufferers with metastatic castration-resistant prostate most cancers (ENZA-p): an open-label, multicentre, randomised, part 2 trial. Lancet Oncol. 25, 563–571 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Baca, S. C. et al. Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate most cancers. Nat. Commun. 12, 1979 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McMullin, R. P. et al. A FOXA1-binding enhancer regulates Hoxb13 expression within the prostate gland. Proc. Natl Acad. Sci. USA 107, 98–103 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Watt, F. et al. A tissue-specific enhancer of the prostate-specific membrane antigen gene, FOLH1. Genomics 73, 243–254 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Giambartolomei, C. et al. H3K27ac HiChIP in prostate cell strains identifies danger genes for prostate most cancers susceptibility. Am. J. Hum. Genet. 108, 2284–2300 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Seifert, R. et al. Evaluation of PSMA expression and consequence in sufferers with superior prostate most cancers receiving 177Lu-PSMA-617 radioligand remedy. Theranostics 10, 7812–7820 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hindié, E. Predicting outcomes after 177Lu-PSMA remedy in castration-resistant prostate most cancers. Lancet Oncol. 22, e425 (2021).

    Article 
    PubMed 

    Google Scholar
     

  • Wang, Z. et al. Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment. Cell Metab. 35, 1209–1226.e1213 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xue, R. et al. Liver tumour immune microenvironment subtypes and neutrophil heterogeneity. Nature 612, 141–147 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schulte, M. L. et al. Pharmacological blockade of ASCT2-dependent glutamine transport results in antitumor efficacy in preclinical fashions. Nat. Med. 24, 194–202 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, Q. et al. Focusing on amino acid transport in metastatic castration-resistant prostate most cancers: results on cell cycle, cell progress, and tumor growth. J. Natl Most cancers Inst. 105, 1463–1473 (2013).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, F., Han, Y. & Kang, Y. Bone marrow niches within the regulation of bone metastasis. Br. J. Most cancers 124, 1912–1920 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Uwe, H., Frederik, G., Alfred, M. & Clemens, Ok. The way forward for radioligand remedy: α, β, or each? J. Nucl. Med. 58, 1017 (2017).

    Article 

    Google Scholar
     

  • Kostos, L. et al. AlphaBet: mixture of radium-223 and [17 7Lu]Lu-PSMA-I&T in males with metastatic castration-resistant prostate most cancers (medical trial protocol). Entrance. Med. 9, 1059122 (2022).

    Article 

    Google Scholar
     

  • Rajasekaran, S. A. et al. A novel cytoplasmic tail MXXXL motif mediates the internalization of prostate-specific membrane antigen. Mol. Biol. Cell 14, 4835–4845 (2003).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ghosh, A. & Heston, W. D. Tumor goal prostate particular membrane antigen (PSMA) and its regulation in prostate most cancers. J. Cell Biochem. 91, 528–539 (2004).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, H. et al. Constitutive and antibody-induced internalization of prostate-specific membrane antigen. Most cancers Res. 58, 4055–4060 (1998).

    CAS 
    PubMed 

    Google Scholar
     

  • Anilkumar, G. et al. Affiliation of prostate-specific membrane antigen with caveolin-1 and its caveolae-dependent internalization in microvascular endothelial cells: implications for concentrating on to tumor vasculature. Microvasc. Res. 72, 54–61 (2006).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Goodman et al. Interplay of prostate particular membrane antigen with clathrin and the adaptor protein complex-2. Int. J. Oncol. 31, 1199–1203 (2007).

    CAS 
    PubMed 

    Google Scholar
     

  • Schmidt, S. et al. Discriminatory function of detergent-resistant membranes within the dimerization and endocytosis of prostate-specific membrane antigen. PLoS ONE 8, e66193 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Anilkumar, G. et al. Prostate-specific membrane antigen affiliation with filamin A modulates its internalization and NAALADase exercise. Most cancers Res. 63, 2645–2648 (2003).

    CAS 
    PubMed 

    Google Scholar
     

  • Christiansen, J. J. et al. N-glycosylation and microtubule integrity are concerned in apical concentrating on of prostate-specific membrane antigen: implications for immunotherapy. Mol. Most cancers Ther. 4, 704–714 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Oudard, S. et al. Cabazitaxel versus docetaxel as first-line remedy for sufferers with metastatic castration-resistant prostate most cancers: a randomized part III trial — FIRSTANA. J. Clin. Oncol. 35, 3189–3197 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kondev, F. G. Nuclear knowledge sheets for A=177. Nucl. Knowledge Sheets 159, 1–412 (2019).

    Article 
    CAS 

    Google Scholar
     

  • Jain, A. Ok., Raut, R. & Tuli, J. Ok. Nuclear knowledge sheets for A = 225. Nucl. Knowledge Sheets 110, 1409–1472 (2009).

    Article 
    CAS 

    Google Scholar
     

  • Kratochwil, C. et al. Focused α-therapy of metastatic castration-resistant prostate most cancers with 225Ac-PSMA-617: dosimetry estimate and empiric dose discovering. J. Nucl. Med. 58, 1624–1631 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Enger, S. A., Hartman, T., Carlsson, J. & Lundqvist, H. Cross-fire doses from β-emitting radionuclides in focused radiotherapy. A theoretical examine primarily based on experimentally measured tumor traits. Phys. Med. Biol. 53, 1909 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • McDevitt, M. R., Sgouros, G. & Sofou, S. Focused and nontargeted α-particle therapies. Annu. Rev. Biomed. Eng. 20, 73–93 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • He, Y. et al. Focusing on signaling pathways in prostate most cancers: mechanisms and medical trials. Sign. Transduct. Goal. Ther. 7, 198 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Enger, S. A., Hartman, T., Carlsson, J. & Lundqvist, H. Cross-fire doses from β-emitting radionuclides in focused radiotherapy. A theoretical examine primarily based on experimentally measured tumor traits. Phys. Med. Biol. 53, 1909–1920 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Azzam, E. I., De Toledo, S. M., Spitz, D. R. & Little, J. B. Oxidative metabolism modulates sign transduction and micronucleus formation in bystander cells from α-particle-irradiated regular human fibroblast cultures. Most cancers Res. 62, 5436–5442 (2002).

    CAS 
    PubMed 

    Google Scholar
     

  • Marie, B. et al. Radiation-induced biologic bystander impact elicited in vitro by focused radiopharmaceuticals labeled with α-, β-, and auger electron-emitting radionuclides. J. Nucl. Med. 47, 1007 (2006).


    Google Scholar
     

  • Bodei, L. et al. The joint IAEA, EANM, and SNMMI sensible steering on peptide receptor radionuclide remedy (PRRNT) in neuroendocrine tumours. Eur. J. Nucl. Med. Mol. Imaging 40, 800–816 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sheehan, B. et al. Prostate-specific membrane antigen expression and response to DNA damaging brokers in prostate most cancers. Clin. Most cancers Res. 28, 3104–3115 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Salas-Ramirez, M. et al. Radiation-induced double-strand breaks by inner ex vivo irradiation of lymphocytes: validation of a Monte Carlo simulation mannequin utilizing GATE and Geant4-DNA. Z. Med. Phys. https://doi.org/10.1016/j.zemedi.2023.07.007 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Khreish, F. et al. 225Ac-PSMA-617/177Lu-PSMA-617 tandem remedy of metastatic castration-resistant prostate most cancers: pilot expertise. Eur. J. Nucl. Med. Mol. Imaging 47, 721–728 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Müller, C. et al. Terbium-161 for PSMA-targeted radionuclide remedy of prostate most cancers. Eur. J. Nucl. Med. Mol. Imaging 46, 1919–1930 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Vlachostergios, P. J. et al. Imaging expression of prostate-specific membrane antigen and response to PSMA-targeted β-emitting radionuclide therapies in metastatic castration-resistant prostate most cancers. Prostate 81, 279–285 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Derlin, T. et al. PSMA-heterogeneity in metastatic castration-resistant prostate most cancers: circulating tumor cells, metastatic tumor burden, and response to focused radioligand remedy. Prostate 83, 1076–1088 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Vanwelkenhuyzen, J. et al. AR and PI3K genomic profiling of cell-free DNA can establish poor responders to lutetium-177-PSMA amongst sufferers with metastatic castration-resistant prostate most cancers. Eur. Urol. Open. Sci. 53, 63–66 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, C.-B. et al. Urine-derived exosomal PSMA is a promising diagnostic biomarker for the detection of prostate most cancers on preliminary biopsy. Clin. Transl. Oncol. 25, 758–767 (2023).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Harmon, S. A. et al. A potential comparability of 18F-sodium fluoride PET/CT and PSMA-targeted 18F-DCFBC PET/CT in metastatic prostate most cancers. J. Nucl. Med. 59, 1665–1671 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Regula, N. et al. Comparability of 68Ga-PSMA-11 PET/CT with 11C-acetate PET/CT in re-staging of prostate most cancers relapse. Sci. Rep. 10, 4993 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shiiba, M. et al. Analysis of major prostate most cancers utilizing 11C-methionine-PET/CT and 18F-FDG-PET/CT. Ann. Nucl. Med. 26, 138–145 (2012).

    Article 
    PubMed 

    Google Scholar
     

  • Zoppolo, F. et al. 11C-SAM: radiosynthesis and preliminary organic research as a possible agent for prostate most cancers prognosis. J. Nucl. Med. 57, 2700–2700 (2016).


    Google Scholar
     

  • Mori, H. et al. Imaging somatostatin receptor exercise in neuroendocrine-differentiated prostate most cancers. Intern. Med. 57, 3123–3128 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Korsen, J. A. et al. Delta-like ligand 3 — focused radioimmunotherapy for neuroendocrine prostate most cancers. Proc. Natl Acad. Sci. USA 119, e2203820119 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kratochwil, C. et al. 68Ga-FAPI PET/CT: tracer uptake in 28 completely different sorts of most cancers. J. Nucl. Med. 60, 801–805 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bakht, M. M. Ok. Molecular imaging targets in prostate cancers with neuroendocrine gene signature. Thesis, Univ. Windsor (Canada) https://scholar.uwindsor.ca/etd/8170 (2019).

  • Uhlen et al. Tissue-based map of the human proteome. Science https://doi.org/10.1126/science.1260419 (2015).

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