Skip to main content

Advertisement

SpringerLink
Log in

Investigation of 90Y-avidin for prostate cancer brachytherapy: a dosimetric model for a phase I–II clinical study

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

Abstract

Purpose

A novel method for prostate irradiation is investigated. Similarly to 125I or 103Pd seed brachytherapy, 90Y-avidin could be injected via the perineum under ultrasound image guidance. This study inspects the theoretical feasibility with a dosimetric model based on Monte Carlo simulation.

Methods

A geometrical model of the prostate, urethra and rectum was designed. The linear-quadratic model was applied to convert 125I absorbed dose prescription/constraints into 90Y dose through biological effective dose (BED) calculation. The optimal 90Y-avidin injection strategy for the present model was obtained. Dose distribution was calculated by Monte Carlo simulation (PENELOPE,GEANT4). Dose volume histograms (DVH) for the prostate, urethra and rectum were compared to typical DVHs of 125I seed brachytherapy, used routinely in our institute.

Results

With 90Y-avidin, at least 95 % of the prostate must receive more than 70 Gy. The absorbed dose to 10 % of the urethra (D10%_urethra) and the maximum absorbed dose to the rectum (Dmax_rectum) must be lower than 122 Gy. For the present model, the optimum strategy consists in multiple injections of 90Y-avidin 50 μl drops, for a total volume of 3.1 ml. The minimum activity to deliver the prescribed absorbed dose is 0.7 GBq, which also fully respects urethral and rectal constraints. The resulting dose map has a maximum in the central region with a sharp decrease towards the urethra and the prostate edge. Notably, D10%_urethra is 95 Gy and Dmax_rectum is below 2 Gy. Prostate absorbed dose is higher with 90Y-avidin than 125I seeds, although the total volume receiving the prescribed absorbed dose is 1–2 % lower. Urethral DVH strictly depends on the 90Y distribution, to be optimized according to prostate shape; in our model, BED30%_urethra is 90 Gy with 90Y-avidin, whereas for patients receiving 125I seeds it ranges between 150 and 230 Gy. The rectal DVH is always more favourable with 90Y.

Conclusion

The methodology is theoretically feasible and can deliver an effective treatment in T1-T2 prostate cancer. Pharmacokinetic and biodistribution studies in prostate cancer patients are needed for validation.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Ash D, Flynn A, Battermann J, de Reijke T, Lavagnini P, Blank L, et al. ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol 2000;57:315–21.

    Article  PubMed  CAS  Google Scholar 

  2. Voulgaris S, Nobes JP, Laing RW, Langley SEM. State-of-the-art: prostate LDR brachytherapy. Prostate Cancer Prostatic Dis 2008;11:237–40.

    Article  PubMed  CAS  Google Scholar 

  3. Taira AV, Merrick GS, Butler WM, Galbreath RW, Lief J, Adamovich E, et al. Long-term outcome for clinically localized prostate cancer treated with permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2011;79(5):1336–42.

    Article  PubMed  Google Scholar 

  4. Stone NN, Stock RG. Reduction of pulmonary migration of permanent interstitial sources in patients undergoing prostate brachytherapy. Urology 2005;66:119–23.

    Article  PubMed  Google Scholar 

  5. Schild MH, Wong WW, Vora SA, Ward LD, Nguyen BD. Embolization of an iodine-125 radioactive seed from the prostate gland into the right ventricle: an unusual pattern of seed migration. Radiography 2009;15:179–81.

    Article  Google Scholar 

  6. Nguyen BD, Schild SE, Wong WW, Vora SA. Prostate brachytherapy seed embolization to the right renal artery. Brachytherapy 2009;8:309–12.

    Article  PubMed  Google Scholar 

  7. Nakano M, Uno H, Gotoh T, Kubota Y, Ishihara S, Deguchi T, et al. Migration of prostate brachytherapy seeds to the vertebral venous plexus. Brachytherapy 2006;5:127–30.

    Article  PubMed  Google Scholar 

  8. Gao M, Wang JZ, Nag S, Gupta N. Effects of seed migration on post-implant dosimetry of prostate brachytherapy. Med Phys 2007;34(2):471–80.

    Article  PubMed  CAS  Google Scholar 

  9. Fuller DB, Koziol JA, Feng AC. Prostate brachytherapy seed migration and dosimetry: analysis of stranded sources and other potential predictive factors. Brachytherapy 2004;3:10–9.

    Article  PubMed  Google Scholar 

  10. Ferrari ME, Cremonesi M, Di Dia A, Botta F, De Cicco C, Sarnelli A, et al. 3D dosimetry in patients with early breast cancer undergoing Intraoperative Avidination for Radionuclide Therapy (IART(®)) combined with external beam radiation therapy. Eur J Nucl Med Mol Imaging 2012;39(11):1702–11.

    Article  PubMed  CAS  Google Scholar 

  11. Paganelli G, Ferrari M, Ravasi L, Cremonesi M, De Cicco C, Galimberti V, et al. Intraoperative avidination for radionuclide therapy: a prospective new development to accelerate radiotherapy in breast cancer. Clin Cancer Res 2007;13:5646s–51s.

    Article  PubMed  CAS  Google Scholar 

  12. Paganelli G, De Cicco C, Ferrari ME, Carbone G, Pagani G, Leonardi MC, et al. Intraoperative avidination for radionuclide treatment as radiotherapy boost in breast cancer: results of a phase II study with (90)Y-labeled biotin. Eur J Nucl Med Mol Imaging 2010;37:203–11.

    Article  PubMed  CAS  Google Scholar 

  13. Urbano N, Papi S, Ginanneschi M, De Santis R, Pace S, Lindstedt R, et al. Evaluation of a new biotin-DOTA conjugate for pretargeted antibody-guided radioimmunotherapy (PAGRIT®). Eur J Nucl Med Mol Imaging 2007;34:68–77.

    Article  PubMed  CAS  Google Scholar 

  14. Chinol M, De Cobelli O, Trifirò G, Scardino E, Bartolomei M, Verweij F, et al. Localization of avidin in superficial bladder cancer: a potentially new approach for radionuclide therapy. Eur Urol 2003;44(5):556–9.

    Article  PubMed  CAS  Google Scholar 

  15. Yao Z, Zhang M, Sakahara H, Saga T, Arano Y, Konishi J. Avidin targeting of intraperitoneal tumor xenografts. J Natl Cancer Inst 1998;90:25–9.

    Article  PubMed  CAS  Google Scholar 

  16. Blasko JC, Mate T, Sylvester JE, Grimm PD, Cavanagh W. Brachytherapy for carcinoma of the prostate: techniques, patient selection, and clinical outcomes. Semin Radiat Oncol 2002;12(1):81–94.

    Article  PubMed  Google Scholar 

  17. Sylvester J, Blasko JC, Grimm P, Ragde H. Interstitial implantation techniques in prostate cancer. J Surg Oncol 1997;66(1):65–75.

    Article  PubMed  CAS  Google Scholar 

  18. Hopkins K, Chandler C, Eatough J, Moss T, Kemshead JT. Direct injection of 90Y MoAbs into glioma tumor resection cavities leads to limited diffusion of the radioimmunoconjugates into normal brain parenchyma: a model to estimate absorbed radiation dose. Int J Radiat Oncol Biol Phys 1998;40(4):835–44.

    Article  PubMed  CAS  Google Scholar 

  19. Salvat F, Fernández-Varea JM, Sempau J. PENELOPE-2008: A code system for Monte Carlo simulation of electron and photon transport. NEA 6416 ISBN 978-92-64-99066-1. 2008. Available via http://www.oecd-nea.org/science/pubs/2009/nea6416-penelope.pdf.

  20. Botta F, Mairani A, Battistoni G, Cremonesi M, Di Dia A, Fassò A, et al. Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for dosimetry in nuclear medicine therapy. Med Phys 2011;38(7):3944–54.

    Article  PubMed  CAS  Google Scholar 

  21. Agostinelli S, Allison J, Amako K, Apostolakis J, Araujo H, Arce P, et al. GEANT4 – a simulation toolkit. Nucl Instrum Methods Phys Res A 2003;506:250–303.

    Article  CAS  Google Scholar 

  22. Carrier JF, Archambault L, Beaulieu L, Roy R. Validation of GEANT4, an object-oriented Monte Carlo toolkit, for simulations in medical physics. Med Phys 2004;31(3):484–92.

    Article  PubMed  CAS  Google Scholar 

  23. Amato E, Lizio D, Settineri N, Di Pasquale A, Salamone I, Pandolfo I. A method to evaluate the dose increase in CT with iodinated contrast medium. Med Phys 2010;37(8):4249–56.

    Article  PubMed  CAS  Google Scholar 

  24. Amato E, Lizio D, Ruggeri RM, Raniolo M, Campennì A, Baldari S. An analytical model for improving absorbed dose calculation accuracy in non spherical autonomous functioning thyroid nodule. Q J Nucl Med Mol Imaging 2011;55(5):560–6.

    PubMed  CAS  Google Scholar 

  25. AAPM Report No. 137, “AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer”. Report of the AAPM Task Group 137.

  26. Fowler J, Chappell RJ, Ritter M. Is α/β for prostate tumors really low? Int J Radiat Oncol Biol Phys 2001;50(4):1021–31.

    Article  PubMed  CAS  Google Scholar 

  27. Fowler J, Ritter MA, Fenwick JD, Chappell RJ. How low is the α/β ratio for prostate cancer? In regard to Wang et al., IJROBP 2003;55:194-203. Int J Radiat Oncol Biol Phys 2003;57(2):593–600.

    Article  PubMed  Google Scholar 

  28. Fowler J. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol 2005;44:265–76.

    Article  PubMed  Google Scholar 

  29. Amato E, Lizio D, Baldari S. Absorbed fractions in ellipsoidal volumes for β− radionuclides employed in internal radiotherapy. Phys Med Biol 2009;54:4171–80.

    Article  PubMed  CAS  Google Scholar 

  30. Amato E, Lizio D, Baldari S. Absorbed fractions for photons in ellipsoidal volumes. Phys Med Biol 2009;54:N479–87.

    Article  PubMed  CAS  Google Scholar 

  31. Amato E, Lizio D, Baldari S. Absorbed fractions for electrons in ellipsoidal volumes. Phys Med Biol 2011;56:357–65.

    Article  PubMed  CAS  Google Scholar 

  32. Takashima R, Egawa S, Kuwao S, Baba S. Anterior distribution of stage T1c nonpalpable tumors in radical prostatectomy specimens. Urology 2002;59(5):692–7.

    Article  PubMed  Google Scholar 

  33. Al-Ahamadie HA, Tickoo SK, Olgac S, Gopalan A, Scardino PT, Reuter VE, et al. Anterior-predominant prostatic tumors: zone of origin and pathologic outcomes at radical prostatectomy. Am J Surg Pathol 2008;32(2):229–35.

    Article  Google Scholar 

  34. Zelefsky MJ, Pei X, Chou JF, Schechter M, Kollmeier M, Cox B, et al. Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes. Eur Urol 2011;60(6):1133–9.

    Article  PubMed  Google Scholar 

  35. Armpilia C, Dale RG, Coles IP, Jones B, Antipas V. The determination of radiobiologically optimized half-lives for radionuclides used in permanent brachytherapy implants. Int J Radiat Oncol Biol Phys 2003;55(2):378–85.

    Article  PubMed  CAS  Google Scholar 

  36. Wang JZ, Guerrero M, Li XA. How low is the α/β ratio for prostate cancer? Int J Radiat Oncol Biol Phys 2003;55(1):194–203.

    Article  PubMed  Google Scholar 

  37. Lhommel R, Goffette P, Van den Eynde M, Jamar F, Pauwels S, Bilbao JI, et al. Yttrium-90 TOF PET scan demonstrates high-resolution biodistribution after liver SIRT. Eur J Nucl Med Mol Imaging 2009;36:1696.

    Article  PubMed  Google Scholar 

  38. Strigari L, Orlandini LC, Andriani I, d’Angelo A, Stefanacci M, Di Nallo AM, et al. A mathematical approach for evaluating the influence of dose heterogeneity on TCP for prostate cancer brachytherapy treatment. Phys Med Biol 2008;53:5045–59.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Medical Physics Unit, European Institute of Oncology, Milan, Italy

    Francesca Botta, Marta Cremonesi, Mahila E. Ferrari, Francesco Guerriero & Guido Pedroli

  2. Radiological Sciences Department, University of Messina, Messina, Italy

    Ernesto Amato

  3. Radiotherapy Division, European Institute of Oncology, Milan, Italy

    Andrea Vavassori

  4. Radiometabolic Unit and Medical Physics Unit, IRCCS IRST, Meldola, Italy

    Anna Sarnelli

  5. Radiometabolic and Nuclear Medicine Unit, IRCCS IRST, Meldola, Italy

    Stefano Severi

  6. Division of Nuclear Medicine, European Institute of Oncology, via Ripamonti 435, 20141, Milan, Italy

    Giovanni Paganelli

Authors
  1. Francesca Botta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marta Cremonesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mahila E. Ferrari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ernesto Amato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco Guerriero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrea Vavassori
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anna Sarnelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stefano Severi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Guido Pedroli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Giovanni Paganelli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Paganelli.

Additional information

A related editorial commentary can be found at doi:10.1007/s00259-013-2413-z.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Botta, F., Cremonesi, M., Ferrari, M.E. et al. Investigation of 90Y-avidin for prostate cancer brachytherapy: a dosimetric model for a phase I–II clinical study. Eur J Nucl Med Mol Imaging 40, 1047–1056 (2013). https://doi.org/10.1007/s00259-013-2383-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00259-013-2383-1

Keywords

Search

Navigation