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. 2009 Jan;2(1):9-17.
doi: 10.2174/1874471010902010009.

Preclinical evaluation of a monoclonal antibody (3C6) specific for prostate-specific membrane antigen

C A S Regino  1 , K J Wong, D E Milenic, E H Holmes, K Garmestani, P L Choyke, M W Brechbiel
Affiliations

Preclinical evaluation of a monoclonal antibody (3C6) specific for prostate-specific membrane antigen

C A S Regino et al. Curr Radiopharm. 2009 Jan.

Abstract

Better tumor markers are needed for early diagnosis and staging of prostate cancer, and for monitoring therapeutic response than the currently used prostate specific antigen (PSA). Prostate specific membrane antigen (PSMA) is highly expressed on the surface of prostatic epithelial cells making it a good target for prostate cancer. In this study, mAb 3C6, specific for the extracellular epitope of PSMA, was evaluated both in vitro and in vivo for PSMA-targeting. Immunoreactivity and specificity of mAb 3C6 was evaluated by flow cytometry using prostate cell lines expressing PSMA such as LNCaP and 22Rv1 and a cell line, DU145, that expresses very little PSMA. 3C6 was conjugated with the acyclic CHX-A" DTPA chelate, radiolabeled with (111)In, and its in vitro and in vivo properties were assessed. The biodistribution of the radioimmunoconjugate evaluated in athymic mice bearing xenografts of three human prostate carcinoma cell lines shows high uptake after 72 hr in LNCaP tumors (%ID/g 22.93 +/- 6.32) and 22Rv1 (%ID/g 10.44 +/- 2.32) in contrast to low uptake by the DU145 tumors (%ID/g 4.27 +/- 0.37). Planar gamma-scintigraphic images obtained for xenografted tumor bearing mice demonstrated targeting for PSMA positive tumors suggesting possible applications in imaging and for targeted radiation therapy.

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Figures

Figure 1
Figure 1
Immunoreactivity of mAb 3C6 with human prostate carcinoma cell lines; mAb 3C6, solid line, isotype control, dotted line.
Figure 2
Figure 2
Size-exclusion HPLC radiochromatogram of 111In-CHX-A”-3C6
Figure 3
Figure 3
Radioimmunoassay evaluating the immunoreactivity of 111In-CHX-A”-3C6. Binding was tested using LNCaP (●), 22Rv1 (△) and DU145 (■).
Figure 4
Figure 4
Planar γ-scintigraphic images obtained at 48, 72, and 168 hr after i.v. injection of 111In-CHX-A”-3C6 in LNCaP, 22Rv1 or DU145-tumor bearing male athymic mouse.
Figure 5
Figure 5
Blood pharmacokinetics for 111In-CHX-A”-3C6 in a LNCaP-tumor bearing male athymic mouse showing the average %ID/mL at each time point. Error bars are reported as standard deviations.
See this image and copyright information in PMC

References

    1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007;57:43. - PubMed
    1. Catalona WJ, Richie JP, Ahmann FR, Hudson MA, Scardino PT, Flanigan RC, deKernion JB, Ratliff TL, Kavoussi LR, Dalkin BL. Comparison of digital rectal examination and serum prostate specific antigen in the early detection of prostate cancer: results of a multicenter clinical trial of 6,630 men. J. Urol. 1994;151:1283. - PubMed
    1. Murphy GP, Barren RJ, Erickson SJ, Bowes VA, Wolfert RL, Bartsch G, Klocker H, Pointner J, Reissigl A, McLeod DG, Douglas T, Morgan T, Kenny GM, Ragde H, Boynton AL, Holmes EH. Evaluation and comparison of two new prostate carcinoma markers. Free-prostate specific antigen and prostate specific membrane antigen. Cancer. 1996;78:809. - PubMed
    1. Thompson IM, Pauler DK, Goodman PJ, Tangen CM, Lucia MS, Parnes HL, Minasian LM, Ford LG, Lippman SM, Crawford ED, Crowley JJ, Coltman CA. Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per milliliter. N. Engl. J. Med. 2004;350:2239. - PubMed
    1. Myrtle JF. Normal levels of prostate-specific antigen (PSA) In: Catalona WJ, Coffey DS, Karr JP, editors. Clinical aspects of prostate cancer: assessment of new diagnostic and management procedures. Elsevier; New York: 1989. pp. 183–189.