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Updated: Apr 24, 2026
MR Molecular Imaging of Prostate Cancer with a Small Molecular CLT1 Peptide Targeted Contrast Agent
Published on: September 3, 2013
Co-targeting androgen receptor and DNA for imaging and molecular radiotherapy of prostate cancer: in vitro studies
Guang Han1, Zbigniew P Kortylewicz, Thomas Enke
1Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Nebraska.
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 (125) IRISAD-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.
Insights
This study introduces 5-Radioiodo-3'-O-(17β-succinyl-5α-androstan-3-one)-2'-deoxyuridin-5'-yl phosphate (RISAD-P) as a theranostic agent for prostate cancer. RISAD-P targets the androgen receptor (AR) for imaging and radiotherapy, showing promise for personalized treatment.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
- Drug Development
Background:
- The androgen receptor (AR) pathway is crucial for prostate cancer growth and survival, making it a key therapeutic target.
- 5-Radioiodo-3 -O-(17 -succinyl-5 -androstan-3-one)-2 -deoxyuridin-5 -yl phosphate (RISAD-P) is an AR-seeking reagent designed for noninvasive assessment and molecular radiotherapy of prostate cancer.
Purpose of the Study:
- To synthesize and evaluate RISAD-P radiolabeled with iodine isotopes (123I, 124I, 125I) for prostate cancer applications.
- To assess the cellular uptake, distribution, and radiotoxicity of RISAD-P in prostate cancer cell lines with varying AR expression levels.
- To explore the potential of RISAD-P as a theranostic agent for imaging AR expression and for targeted radiotherapy.
Main Methods:
- Synthesis of RISAD-P radiolabeled with 123I, 124I, and 125I using a common stannylated precursor.
- Measurement of cellular uptake, subcellular distribution, and radiotoxicity of radiolabeled RISAD-P in LNCaP, DU145, and PC-3 cell lines.
- Quantification of AR expression levels in different cell lines.
Main Results:
- RISAD-P uptake by prostate cancer cells was directly proportional to AR levels and independent of the radionuclide.
- Intracellular radioactivity accumulated in proportion to extracellular RISAD-P concentration and exposure duration, initially in the cytoplasm and later associated with DNA.
- RISAD-P demonstrated significant radiotoxicity, particularly in AR-high LNCaP cells, leading to up to 60% cell kill per day. AR expression was quantified in AR-negative cell lines (PC-3, DU145) using this method.
Conclusions:
- RISAD-P functions as a theranostic drug targeting the androgen receptor (AR) in prostate cancer.
- Its metabolite integrates into DNA synthesis, contributing to its therapeutic effect.
- RISAD-P shows significant promise for imaging AR expression, assessing tumor proliferation, and for molecular radiotherapy of prostate cancer.
