Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter

C. Spitzweg, M. K. O'Connor, E. R. Bergert, D. J. Tindall, C. Y F Young, J. C. Morris

Research output: Contribution to journalArticle

186 Citations (Scopus)

Abstract

Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) by targeted NIS gene transfer might offer the possibility of radioiodine therapy of prostate cancer. Therefore, we investigated radioiodine accumulation and therapeutic effectiveness of 131I in NIS-transfected prostate cancer cells in vitro and in vivo. The human prostatic adenocarcinoma cell line LNCaP was stably transfected with NIS cDNA under the control of the prostate-specific antigen promoter. The stably transfected LNCaP cell line NP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in vitro that resulted in selective killing of these cells by 131I in an in vitro clonogenic assay. Xenografts were established in athymic nude mice and imaged using a gamma camera after i.p. injection of 500 μCi of 123I. In contrast to the NIS-negative control tumors (P-1) which showed no in vivo uptake of 123I, NP-1 tumors accumulated 25-30% of the total 123I administered with a biological half-life of 45 h. In addition, NIS protein expression in LNCaP cell xenografts was confirmed by Western blot analysis and immunohistochemistry. After a single i.p. application of a therapeutic 131I dose (3 mCi), significant tumor reduction was achieved in NP-1 tumors in the therapy group compared with P-1 tumors and tumors in the control group. In conclusion, a therapeutic effect of 131I has been demonstrated in prostate cancer cells after induction of tissue-specific iodide uptake activity by prostate-specific antigen promoter-directed NIS expression in vitro and in vivo. This study demonstrates the potential of NIS as a novel therapeutic gene for nonthyroidal cancers, in particular prostate cancer.

Original languageEnglish (US)
Pages (from-to)6526-6530
Number of pages5
JournalCancer Research
Volume60
Issue number22
StatePublished - 2000

Fingerprint

Cell- and Tissue-Based Therapy
Prostatic Neoplasms
Neoplasms
Iodides
Prostate-Specific Antigen
Heterografts
Nude Mice
Therapeutics
Cell Line
Gamma Cameras
Neoplasm Genes
Therapeutic Uses
Group Psychotherapy
Androgens
Half-Life
sodium-iodide symporter
Adenocarcinoma
Complementary DNA
Western Blotting
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Spitzweg, C., O'Connor, M. K., Bergert, E. R., Tindall, D. J., Young, C. Y. F., & Morris, J. C. (2000). Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Research, 60(22), 6526-6530.

Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. / Spitzweg, C.; O'Connor, M. K.; Bergert, E. R.; Tindall, D. J.; Young, C. Y F; Morris, J. C.

In: Cancer Research, Vol. 60, No. 22, 2000, p. 6526-6530.

Research output: Contribution to journalArticle

Spitzweg, C, O'Connor, MK, Bergert, ER, Tindall, DJ, Young, CYF & Morris, JC 2000, 'Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter', Cancer Research, vol. 60, no. 22, pp. 6526-6530.
Spitzweg C, O'Connor MK, Bergert ER, Tindall DJ, Young CYF, Morris JC. Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. Cancer Research. 2000;60(22):6526-6530.
Spitzweg, C. ; O'Connor, M. K. ; Bergert, E. R. ; Tindall, D. J. ; Young, C. Y F ; Morris, J. C. / Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter. In: Cancer Research. 2000 ; Vol. 60, No. 22. pp. 6526-6530.
@article{c19058a2cb26415c9379c252fb5f1c18,
title = "Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter",
abstract = "Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) by targeted NIS gene transfer might offer the possibility of radioiodine therapy of prostate cancer. Therefore, we investigated radioiodine accumulation and therapeutic effectiveness of 131I in NIS-transfected prostate cancer cells in vitro and in vivo. The human prostatic adenocarcinoma cell line LNCaP was stably transfected with NIS cDNA under the control of the prostate-specific antigen promoter. The stably transfected LNCaP cell line NP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in vitro that resulted in selective killing of these cells by 131I in an in vitro clonogenic assay. Xenografts were established in athymic nude mice and imaged using a gamma camera after i.p. injection of 500 μCi of 123I. In contrast to the NIS-negative control tumors (P-1) which showed no in vivo uptake of 123I, NP-1 tumors accumulated 25-30{\%} of the total 123I administered with a biological half-life of 45 h. In addition, NIS protein expression in LNCaP cell xenografts was confirmed by Western blot analysis and immunohistochemistry. After a single i.p. application of a therapeutic 131I dose (3 mCi), significant tumor reduction was achieved in NP-1 tumors in the therapy group compared with P-1 tumors and tumors in the control group. In conclusion, a therapeutic effect of 131I has been demonstrated in prostate cancer cells after induction of tissue-specific iodide uptake activity by prostate-specific antigen promoter-directed NIS expression in vitro and in vivo. This study demonstrates the potential of NIS as a novel therapeutic gene for nonthyroidal cancers, in particular prostate cancer.",
author = "C. Spitzweg and O'Connor, {M. K.} and Bergert, {E. R.} and Tindall, {D. J.} and Young, {C. Y F} and Morris, {J. C.}",
year = "2000",
language = "English (US)",
volume = "60",
pages = "6526--6530",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - Treatment of prostate cancer by radioiodine therapy after tissue-specific expression of the sodium iodide symporter

AU - Spitzweg, C.

AU - O'Connor, M. K.

AU - Bergert, E. R.

AU - Tindall, D. J.

AU - Young, C. Y F

AU - Morris, J. C.

PY - 2000

Y1 - 2000

N2 - Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) by targeted NIS gene transfer might offer the possibility of radioiodine therapy of prostate cancer. Therefore, we investigated radioiodine accumulation and therapeutic effectiveness of 131I in NIS-transfected prostate cancer cells in vitro and in vivo. The human prostatic adenocarcinoma cell line LNCaP was stably transfected with NIS cDNA under the control of the prostate-specific antigen promoter. The stably transfected LNCaP cell line NP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in vitro that resulted in selective killing of these cells by 131I in an in vitro clonogenic assay. Xenografts were established in athymic nude mice and imaged using a gamma camera after i.p. injection of 500 μCi of 123I. In contrast to the NIS-negative control tumors (P-1) which showed no in vivo uptake of 123I, NP-1 tumors accumulated 25-30% of the total 123I administered with a biological half-life of 45 h. In addition, NIS protein expression in LNCaP cell xenografts was confirmed by Western blot analysis and immunohistochemistry. After a single i.p. application of a therapeutic 131I dose (3 mCi), significant tumor reduction was achieved in NP-1 tumors in the therapy group compared with P-1 tumors and tumors in the control group. In conclusion, a therapeutic effect of 131I has been demonstrated in prostate cancer cells after induction of tissue-specific iodide uptake activity by prostate-specific antigen promoter-directed NIS expression in vitro and in vivo. This study demonstrates the potential of NIS as a novel therapeutic gene for nonthyroidal cancers, in particular prostate cancer.

AB - Causing prostate cancer cells to express functionally active sodium iodide symporter (NIS) by targeted NIS gene transfer might offer the possibility of radioiodine therapy of prostate cancer. Therefore, we investigated radioiodine accumulation and therapeutic effectiveness of 131I in NIS-transfected prostate cancer cells in vitro and in vivo. The human prostatic adenocarcinoma cell line LNCaP was stably transfected with NIS cDNA under the control of the prostate-specific antigen promoter. The stably transfected LNCaP cell line NP-1 showed perchlorate-sensitive, androgen-dependent iodide uptake in vitro that resulted in selective killing of these cells by 131I in an in vitro clonogenic assay. Xenografts were established in athymic nude mice and imaged using a gamma camera after i.p. injection of 500 μCi of 123I. In contrast to the NIS-negative control tumors (P-1) which showed no in vivo uptake of 123I, NP-1 tumors accumulated 25-30% of the total 123I administered with a biological half-life of 45 h. In addition, NIS protein expression in LNCaP cell xenografts was confirmed by Western blot analysis and immunohistochemistry. After a single i.p. application of a therapeutic 131I dose (3 mCi), significant tumor reduction was achieved in NP-1 tumors in the therapy group compared with P-1 tumors and tumors in the control group. In conclusion, a therapeutic effect of 131I has been demonstrated in prostate cancer cells after induction of tissue-specific iodide uptake activity by prostate-specific antigen promoter-directed NIS expression in vitro and in vivo. This study demonstrates the potential of NIS as a novel therapeutic gene for nonthyroidal cancers, in particular prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=0033693586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033693586&partnerID=8YFLogxK

M3 - Article

C2 - 11103823

AN - SCOPUS:0033693586

VL - 60

SP - 6526

EP - 6530

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 22

ER -