Skip to main content
SpringerLink
Log in

Positron tomographic assessment of androgen receptors in prostatic carcinoma

  • Molecular Imaging
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16β-[18F]fluoro-5α-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer.

Methods

Twenty men (age range 56–87 years) with advanced prostate cancer were studied. All except one had metastatic disease confirmed by biopsy and/or radiological studies. One patient who had radiological findings suggesting a single hepatic metastasis was found to have focal fatty infiltration on biopsy obtained after FDHT-PET and was excluded from further data analysis. FDHT uptake was assessed semiquantitatively by determination of the standardized uptake value (SUV) and tumor-to-muscle ratio (T/M). Additionally, to assess the AR binding selectivity of FDHT, patients with one or more foci of abnormally increased FDHT accumulation were studied after administration of an AR antagonist (flutamide).

Results

Conventional imaging demonstrated innumerable lesions in two patients and 43 lesions in the remaining 17 patients with advanced prostate cancer. FDHT-PET was positive in 12 of 19 patients (sensitivity of 63%), including the two patients with innumerable lesions. FDHT-PET detected 24 of 28 known lesions (86%) in the remaining ten patients. In addition, FDHT-PET detected 17 unsuspected lesions in five of these ten patients. All 12 patients with positive FDHT-PET underwent a repeat PET study after receiving flutamide for 1 day (250 mg t.i.d.). In all of these patients, there was a decrease in tumor FDHT uptake after flutamide; the mean (± standard deviation) SUV and T/M decreased from 7.0±4.7 and 6.9±3.9, respectively, to 3.0±1.5 and 3.0±1.6, respectively (p=0.002). The mean PSA in patients with positive FDHT-PET was significantly higher than that in patients with negative FDHT-PET (p=0.006).

Conclusion

Our results document the feasibility of PET imaging of prostate cancer with FDHT and suggest that tumor uptake of FDHT is a receptor-mediated process. Positive PET studies were associated with higher PSA levels and thus, presumably, with greater tumor burden.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Huggins C. The effect of castration, of estrogen and of androgen injections on serum phosphatases in metastatic carcinoma of the prostate: studies on prostate cancer. Cancer Res 1941;1:293–7.

    Google Scholar 

  2. Buchanan G, Irvine RA, Coetzee GA, Tilley WD. Contribution of the androgen receptor to prostate cancer predisposition and progression. Cancer Metastasis Rev 2001;20:207–23.

    Article  Google Scholar 

  3. Loblaw DA, Mendelson DS, Talcott JA, Virgo KS, Somerfield MR, Ben-Josef E, et al. American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer. J Clin Oncol 2004;22:2927–41.

    Google Scholar 

  4. Mintun MA, Welch MJ, Siegel BA, Mathias CJ, Brodack JW, McGuire AH, et al. Breast cancer: PET imaging of estrogen receptors. Radiology 1988;169:45–8.

    CAS  PubMed  Google Scholar 

  5. McGuire AH, Dehdashti F, Siegel BA, Lyss AP, Brodack JW, Mathias CJ, et al. Positron tomographic assessment of 16α-[18F]fluoro-17β-estradiol uptake in metastatic breast carcinoma. J Nucl Med 1991;32:1526–31.

    CAS  PubMed  Google Scholar 

  6. Dehdashti F, McGuire AH, Van Brocklin HF, Siegel BA, Andriole DP, Griffeth LK, et al. Assessment of 21-[18F]fluoro-16 α-ethyl-19-norprogesterone as a positron-emitting radiopharmaceutical for the detection of progestin receptors in human breast carcinomas. J Nucl Med 1991;32:1532–7.

    CAS  PubMed  Google Scholar 

  7. Dehdashti F, Mortimer JE, Siegel BA, Griffeth LK, Bonasera TJ, Fusselman MJ, et al. Positron tomographic assessment of estrogen receptors in breast cancer. Comparison with FDG-PET and in vitro receptor assays. J Nucl Med 1995;36:1766–74.

    CAS  PubMed  Google Scholar 

  8. Dehdashti F, Flanagan FL, Mortimer JE, Katzenellenbogen JA, Welch MJ, Siegel BA. PET assessment of “metabolic flare” to predict response of metastatic breast cancer to antiestrogen therapy. Eur J Nucl Med 1999;26:51–6.

    Article  CAS  PubMed  Google Scholar 

  9. Mortimer JE, Dehdashti F, Siegel BA, Katzenellenbogen JA, Fracasso P, Welch MJ. Positron emission tomography with 2-[18F]fluoro-2-deoxy-d-glucose and 16α-[18F]fluoro-17β-estradiol in breast cancer: correlation with estrogen receptor status and response to systemic therapy. Clin Cancer Res 1996;2:933–9.

    Google Scholar 

  10. Bonasera TA, O‘Neil JP, Xu M, Dobkin JA, Cutler PD, Lich LL, et al. Preclinical evaluation of fluorine-18-labeled androgen receptor ligands in baboons. J Nucl Med 1996;37:1009–15.

    CAS  PubMed  Google Scholar 

  11. Liu A, Dence CS, Welch MJ, Katzenellenbogen JA. Fluorine-18-labeled androgens: radiochemical synthesis and tissue distribution studies on six fluorine-substituted androgens, potential imaging agents for prostatic cancer. J Nucl Med 1992;33:724–34.

    CAS  PubMed  Google Scholar 

  12. Kubota K, Matsuzawa T, Ito M, Ito K, Fujiwara T, Abe Y, et al. Lung tumor imaging by positron emission tomography using C-11 L-methionine. J Nucl Med 1985;26:37–42.

    Google Scholar 

  13. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, et al. Cancer statistics 2005. CA Cancer J Clin 2005;55:10–30.

    Google Scholar 

  14. Thenot S, Charpin M, Bonnet S, Cavailles V. Estrogen receptor cofactors expression in breast and endometrial human cancer cells. Mol Cell Endocrinol 1999;156:85–93.

    Article  Google Scholar 

  15. Kozlowski JM, Ellis WJ, Grayhack JT. Advanced prostatic carcinoma. Early versus late endocrine therapy. Urol Clin North Am 1991;18:15–24.

    Google Scholar 

  16. Hyytinen ER, Haapala K, Thompson J, Lappalainen I, Roiha M, Rantala I, et al. Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer. Lab Invest 2002;82:1591–8.

    Google Scholar 

  17. Wong CI, Zhou ZX, Sar M, Wilson EM. Steroid requirement for androgen receptor dimerization and DNA binding. Modulation by intramolecular interactions between the NH2-terminal and steroid-binding domains. J Biol Chem 1993;268:19004–12.

    Google Scholar 

  18. Culig Z, Hobisch A, Hittmair A, Peterziel H, Cato AC, Bartsch G, et al. Expression, structure, and function of androgen receptor in advanced prostatic carcinoma. Prostate 1998;35:63–70.

    Article  Google Scholar 

  19. Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and over expression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res 2001;61:3550–5.

    Google Scholar 

  20. Yeh S, Lin HK, Kang HY, Thin TH, Lin MF, Chang C. From HER2/Neu signal cascade to androgen receptor and its coactivators: a novel pathway by induction of androgen target genes through MAP kinase in prostate cancer cells. Proc Natl Acad Sci U S A 1999;96:5458–63.

    Article  Google Scholar 

  21. Bentel JM, Tilley WD. Androgen receptors in prostate cancer. J Endocrinol 1996;151:1–11.

    Article  Google Scholar 

  22. Sadar MD, Hussain M, Bruchovsky N. Prostate cancer: molecular biology of early progression to androgen independence. Endocr Relat Cancer 1999;6:487–502.

    Article  Google Scholar 

  23. Jenster G. The role of the androgen receptor in the development and progression of prostate cancer. Semin Oncol 1999;26:407–21.

    Google Scholar 

  24. Larson SM, Morris M, Gunther I, Beattie B, Humm JL, Akhurst TA, et al. Tumor localization of 16β-18F-fluoro-5α-dihydrotestosterone versus 18F-FDG in patients with progressive, metastatic prostate cancer. J Nucl Med 2004;45:366–73.

    Google Scholar 

Download references

Acknowledgments

This work was supported by Department of Energy grants DE-FG02-86ER60401 and DE-FG0284ER60218.

Author information

Authors and Affiliations

  1. The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Farrokh Dehdashti, Joel Picus, Jeff M. Michalski, Barry A. Siegel & Michael J. Welch

  2. Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Joel Picus

  3. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Jeff M. Michalski

  4. Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Farrokh Dehdashti, Carmen S. Dence, Barry A. Siegel & Michael J. Welch

  5. Department of Chemistry, University of Illinois, Urbana, IL, 61801, USA

    John A. Katzenellenbogen

Authors
  1. Farrokh Dehdashti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joel Picus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeff M. Michalski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carmen S. Dence
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Barry A. Siegel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John A. Katzenellenbogen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael J. Welch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farrokh Dehdashti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dehdashti, F., Picus, J., Michalski, J.M. et al. Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur J Nucl Med Mol Imaging 32, 344–350 (2005). https://doi.org/10.1007/s00259-005-1764-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-005-1764-5

Keywords

Search

Navigation