Investigation of (90)Y-avidin for prostate cancer brachytherapy: A dosimetric model for a phase I–II clinical study, "Beyond the Abstract," by Giovanni Paganelli, MD

BERKELEY, CA (UroToday.com) - According to international recommendations, interstitial permanent brachytherapy with radioactive seeds is considered an established treatment option for low-risk prostate cancer.[1, 2] However, seed migration is a potential well-recognized side-effect due to the fact that the radioactive sources are small enough to migrate through the venous plexus surrounding the prostate gland. The increased use of brachytherapy has led to several reports addressing the risk of seed embolization. The most frequent site of migration is the lung,[3] although rare migrations have been reported to the heart,[4] the kidney,[5] and the vertebral venous plexus.[6] Seeds lost to migration detract from the overall dose expected to cover the prostate volume with dosimetric detrimental consequences and a potential change in the effectiveness of treatment. An optimal absorbed dose distribution is a critical determinant of successful results with permanent seed implantation.

In our recent article, a new therapeutic approach is considered based on multiple injections of 90Y labelled avidin in small volumes (drops), designed to maximize the uniformity of radiopharmaceutical distribution, and, at the same time, the irradiation of the gland as already reported for breast cancer.[7]

90Y-avidin can be injected into the prostate using a device similar to that used for seed implantation during interstitial brachytherapy. While the 90Y-avidin calculations do not refer to a real patient, at this stage these results are enough to confirm that the proposed methodology is theoretically feasible, having the potential to provide a good treatment. Obviously, experimental measurements are needed to verify the practical feasibility of the injection procedure and the validity of the assumptions underlying the model.

When planning a treatment in the clinical practice, for a real patient, it will be fundamental to consider different isotopes and different injection strategies, and to compare the DVHs from competitive plans to identify the best treatment option. In this study, the dosimetric results, obtained by Monte Carlo simulation, were compared to typical performances of 125I-seed brachytherapy procedures.

Both the “maximum injectable activity” and the “minimum required activity” of 90Y-avidin deliver much higher absorbed doses to the gland with respect to 125I brachytherapy. The urethra irradiation is likely to be more favourable with 90Y-avidin rather than 125I seeds. The rectum is completely spared with 90Y-avidin injection. There are also radiobiological considerations supporting the use of 90Y-avidin for prostate therapy, especially in case of tumours with fairly high repopulation rates. When the repopulation rate is high, radionuclides with small half-lives are more desirable, since they deliver a higher initial dose rate and thus better compensate the repopulation effect. In some situations, particularly if the tumour α/β ratio is lower than the normal tissue, the optimum half-life can be lower than 100 hours, making 90Y (64 hours half-life) preferable to 125I (1440 hours half-life). Pharmacokinetics and biodistribution clinical studies are needed to validate the assumptions underlying this model and to assess the new method in clinical practice.

References:

  1. Ash D, Flynn A, Battermann J, de Reijke T, Lavagnini P, Blank L. ESTRO/EAU/EORTC recommendations on permanent seed implantation for localized prostate cancer. Radiother Oncol. 2000;57:315–21.
  2. Taira AV, Merrick GS, Butler WM, Galbreath RW, Lief J, Adamovich E, Wallner KE. Long-term outcome for clinically localized prostate cancer treated with permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys. 2011;79(5):1336-42.
  3. Stone NN, Stock RG. Reduction of pulmonary migration of permanent interstitial sources in patients undergoing prostate brachytherapy. Urology. 2005;66:119-23.
  4. Schild MH, Wong WW, Vora SA, Ward LD, Nguyen BaD. 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.
  5. Nguyen BaD, Schild SE, Wong WW, Vora SA. Prostate brachytherapy seed embolization to the right renal artery. Brachytherapy. 2009;8:309-12.
  6. Nakano M, Uno H, Gotoh T, Kubota Y, Ishihara S, Deguchi T, Hayashi S, Matsuo M, Tanaka O, Hoshi H. Migration of prostate brachytherapy seeds to the vertebral venous plexus. Brachytherapy. 2006;5:127-30.
  7. 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.

Written by:
Giovanni Paganelli, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Nuclear Medicine Division, European Institute of Oncology, Milan, Italy and Radiometabolic Unit, IRST, Meldola, Italy

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

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