Co-targeting androgen receptor and DNA for imaging and molecular radiotherapy of prostate cancer: In vitro studies

Guang Han, Zbigniew P. Kortylewicz, Thomas Enke, Janina Baranowska-Kortylewicz

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


BACKGROUND The androgen receptor (AR) axis, the key growth and survival pathway in prostate cancer, remains a prime target for drug development. 5-Radioiodo-3′-O-(17β-succinyl-5α-androstan-3-one)-2′-deoxyuridin-5′-yl phosphate (RISAD-P) is the AR-seeking reagent developed for noninvasive assessment of AR and proliferative status, and for molecular radiotherapy of prostate cancer with Auger electron-emitting radionuclides. METHODS RISAD-P radiolabeled with 123I, 124I, and 125I were synthesized using a common stannylated precursor. The cellular uptake, subcellular distribution, and radiotoxicity of 123I-, 124I-, and 125IRISAD-P were measured in LNCaP, DU145, and PC-3 cell lines expressing various levels of AR. RESULTS The uptake of RISAD-P by prostate cancer cells is proportional to AR levels and independent of the radionuclide. The intracellular accumulation of radioactivity is directly proportional to the extracellular concentration of RISAD-P and the duration of exposure. Initially, RISAD-P is trapped in the cytoplasm. Within 24 hr, radioactivity is associated exclusively with DNA. The RISAD-P radiotoxicity is determined by the radionuclide; however, the cellular responses are directly proportional to the AR expression levels. LNCaP cells expressing high levels of AR are killed at the rate of up to 60% per day after a brief 1 hr RISAD-P treatment. For the first time, the AR expression in PC-3 and DU 145 cells, generally reported as AR-negative, was quantitated by the ultra sensitive RISAD-P-based method. CONCLUSIONS RISAD-P is a theranostic drug, which targets AR. Its subcellular metabolite participates in DNA synthesis. RISAD-P is a promising candidate for imaging of the AR expression and tumor proliferation as well as molecular radiotherapy of prostate cancer.

Original languageEnglish (US)
Pages (from-to)1634-1646
Number of pages13
Issue number16
StatePublished - Dec 1 2014


  • Auger electrons
  • androgen receptor
  • molecular radiotherapy
  • prostate cancer
  • theranostic

ASJC Scopus subject areas

  • Oncology
  • Urology


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