Design, Synthesis, and Preclinical Evaluation of Prostate-specific Membrane Antigen Targeted (99m)Tc-radioimaging Agents

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2009 Apr 14

PMID 19361232

Citations 65

Authors

Sumith A Kularatne

Zhigang Zhou

Jun Yang

Carol B Post

Philip S Low

Affiliations

Soon will be listed here.

Abstract

The high mortality and financial burden associated with prostate cancer can be partly attributed to a lack of sensitive screening methods for detection and staging of the disease. Guided by in silico docking studies using the crystal structure of PSMA, we designed and synthesized a series of PSMA-targeted (99m)Tc-chelate complexes for imaging PSMA-expressing human prostate cancer cells (LNCaP cell line). Of the six targeted radioimaging agents synthesized, three were found to bind LNCaP cells with low nanomolar affinity. Moreover, the same three PSMA-targeted imaging agents were shown to localize primarily to LNCaP tumor xenografts in nu/nu mice, with an average of 9.8 +/- 2.4% injected dose/g tissue accumulating in the tumor and only 0.11% injected dose/g tissue retained in the muscle at 4 h postinjection. Collectively, these high affinity, PSMA-specific radioimaging agents demonstrate significant potential for use in localizing prostate cancer masses, monitoring response to therapy, detecting prostate cancer recurrence following surgery, and selecting patients for subsequent PSMA-targeted chemotherapy.

Citing Articles

Selective targeting of chemically modified miR-34a to prostate cancer using a small molecule ligand and an endosomal escape agent.

Abdelaal A, Sohal I, Iyer S, Sudarshan K, Orellana E, Ozcan K Mol Ther Nucleic Acids. 2024; 35(2):102193.

PMID: 38745855 PMC: 11091501. DOI: 10.1016/j.omtn.2024.102193.

Recent advances in the development of Ac- and At-labeled radioligands for radiotheranostics.

Munekane M, Fuchigami T, Ogawa K Anal Sci. 2024; 40(5):803-826.

PMID: 38564087 PMC: 11035452. DOI: 10.1007/s44211-024-00514-w.

The Preparation and Execution of Exploratory Human Studies on Novel Tc-Labeled Glucosamine Derivatives Containing Different Phenyl Isonitriles as Promising Tumor Imaging Agents.

Wang Q, Gan Q, Jiang Y, Xiao D, Chen X, Zhang J ACS Pharmacol Transl Sci. 2023; 6(11):1681-1691.

PMID: 37974617 PMC: 10644395. DOI: 10.1021/acsptsci.3c00146.

Synthesis, I-Radiolabeling Optimization, and Initial Preclinical Evaluation of Novel Urea-Based PSMA Inhibitors with a Tributylstannyl Prosthetic Group in Their Structures.

Hasnowo L, Larkina M, Plotnikov E, Bodenko V, Yuldasheva F, Stasyuk E Int J Mol Sci. 2023; 24(15).

PMID: 37569582 PMC: 10418939. DOI: 10.3390/ijms241512206.

Preclinical Evaluation of a PSMA-Targeting Homodimer with an Optimized Linker for Imaging of Prostate Cancer.

Murce E, Beekman S, Spaan E, Handula M, Stuurman D, de Ridder C Molecules. 2023; 28(10).

PMID: 37241763 PMC: 10223019. DOI: 10.3390/molecules28104022.

References

Ghosh A, Heston W . Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004; 91(3):528-39. DOI: 10.1002/jcb.10661. View

Tasch J, Gong M, Sadelain M, Heston W . A unique folate hydrolase, prostate-specific membrane antigen (PSMA): a target for immunotherapy?. Crit Rev Immunol. 2001; 21(1-3):249-61. View

Banerjee S, Foss C, Castanares M, Mease R, Byun Y, Fox J . Synthesis and evaluation of technetium-99m- and rhenium-labeled inhibitors of the prostate-specific membrane antigen (PSMA). J Med Chem. 2008; 51(15):4504-17. PMC: 3336105. DOI: 10.1021/jm800111u. View

Troyer J, Beckett M, Wright Jr G . Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int J Cancer. 1995; 62(5):552-8. DOI: 10.1002/ijc.2910620511. View

Kawakami M, Nakayama J . Enhanced expression of prostate-specific membrane antigen gene in prostate cancer as revealed by in situ hybridization. Cancer Res. 1997; 57(12):2321-4. View

Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V . Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res. 1997; 57(17):3629-34. View

Chodak G, Keller P, SCHOENBERG H . Assessment of screening for prostate cancer using the digital rectal examination. J Urol. 1989; 141(5):1136-8. DOI: 10.1016/s0022-5347(17)41192-x. View

Seccamani E, Tattanelli M, Mariani M, Spranzi E, SCASSELLATI G, Siccardi A . A simple qualitative determination of human antibodies to murine immunoglobulins (HAMA) in serum samples. Int J Rad Appl Instrum B. 1989; 16(2):167-70. DOI: 10.1016/0883-2897(89)90191-8. View

Kozikowski A, Nan F, Conti P, Zhang J, Ramadan E, Bzdega T . Design of remarkably simple, yet potent urea-based inhibitors of glutamate carboxypeptidase II (NAALADase). J Med Chem. 2001; 44(3):298-301. DOI: 10.1021/jm000406m. View

10.

Colcher D, Bird R, Roselli M, HARDMAN K, Johnson S, Pope S . In vivo tumor targeting of a recombinant single-chain antigen-binding protein. J Natl Cancer Inst. 1990; 82(14):1191-7. DOI: 10.1093/jnci/82.14.1191. View

11.

Chang S, OKeefe D, Bacich D, Reuter V, Heston W, Gaudin P . Prostate-specific membrane antigen is produced in tumor-associated neovasculature. Clin Cancer Res. 1999; 5(10):2674-81. View

12.

Jackson P, Slusher B . Design of NAALADase inhibitors: a novel neuroprotective strategy. Curr Med Chem. 2001; 8(8):949-57. DOI: 10.2174/0929867013372797. View

13.

Sodee D, Ellis R, Samuels M, Spirnak J, Poole W, Riester C . Prostate cancer and prostate bed SPECT imaging with ProstaScint: semiquantitative correlation with prostatic biopsy results. Prostate. 1998; 37(3):140-8. DOI: 10.1002/(sici)1097-0045(19981101)37:3<140::aid-pros3>3.0.co;2-q. View

14.

Essink-Bot M, de Koning H, Nijs H, Kirkels W, van der Maas P, Schroder F . Short-term effects of population-based screening for prostate cancer on health-related quality of life. J Natl Cancer Inst. 1998; 90(12):925-31. DOI: 10.1093/jnci/90.12.925. View

15.

Slusher B, Tsai G, Yoo G, Coyle J . Immunocytochemical localization of the N-acetyl-aspartyl-glutamate (NAAG) hydrolyzing enzyme N-acetylated alpha-linked acidic dipeptidase (NAALADase). J Comp Neurol. 1992; 315(2):217-29. DOI: 10.1002/cne.903150208. View

16.

Mease R, Dusich C, Foss C, Ravert H, Dannals R, Seidel J . N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-L-cysteine, [18F]DCFBC: a new imaging probe for prostate cancer. Clin Cancer Res. 2008; 14(10):3036-43. PMC: 3078104. DOI: 10.1158/1078-0432.CCR-07-1517. View

17.

Wright Jr G, Grob B, Haley C, Grossman K, Newhall K, Petrylak D . Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy. Urology. 1996; 48(2):326-34. DOI: 10.1016/s0090-4295(96)00184-7. View

18.

Linn M, Ball R, Maradiegue A . Prostate-specific antigen screening: friend or foe?. Urol Nurs. 2008; 27(6):481-9. View

19.

Kularatne S, Wang K, Santhapuram H, Low P . Prostate-specific membrane antigen targeted imaging and therapy of prostate cancer using a PSMA inhibitor as a homing ligand. Mol Pharm. 2009; 6(3):780-9. DOI: 10.1021/mp900069d. View

20.

Lopes A, Davis W, Rosenstraus M, Uveges A, Gilman S . Immunohistochemical and pharmacokinetic characterization of the site-specific immunoconjugate CYT-356 derived from antiprostate monoclonal antibody 7E11-C5. Cancer Res. 1990; 50(19):6423-9. View