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Tumor Dosimetry Using [124I]m-iodobenzylguanidine MicroPET/CT for [131I]m-iodobenzylguanidine Treatment of Neuroblastoma in a Murine Xenograft Model

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Abstract

Purpose

[124I]m-iodobenzylguanidine (124I-mIBG) provides a quantitative tool for pretherapy tumor imaging and dosimetry when performed before [131I]m-iodobenzylguanidine (131I-mIBG) targeted radionuclide therapy of neuroblastoma. 124I (T 1/2 = 4.2 days) has a comparable half-life to that of 131I (T 1/2 = 8.02 days) and can be imaged by positron emission tomography (PET) for accurate quantification of the radiotracer distribution. We estimated expected radiation dose in tumors from 131I-mIBG therapy using 124I-mIBG microPET/CT imaging data in a murine xenograft model of neuroblastoma transduced to express high levels of the human norepinephrine transporter (hNET).

Procedures

In order to enhance mIBG uptake for in vivo imaging and therapy, NB 1691-luciferase (NB1691) human neuroblastoma cells were engineered to express high levels of hNET protein by lentiviral transduction (NB1691-hNET). Both NB1691 and NB1691-hNET cells were implanted subcutaneously and into renal capsules in athymic mice. 124I-mIBG (4.2–6.5 MBq) was administered intravenously for microPET/CT imaging at 5 time points over 95 h (0.5, 3–5, 24, 48, and 93–95 h median time points). In vivo biodistribution data in normal organs, tumors, and whole-body were collected from reconstructed PET images corrected for photon attenuation using the CT-based attenuation map. Organ and tumor dosimetry were determined for 124I-mIBG. Dose estimates for 131I-mIBG were made, assuming the same in vivo biodistribution as 124I-mIBG.

Results

All NB1691-hNET tumors had significant uptake and retention of 124I-mIBG, whereas unmodified NB1691 tumors did not demonstrate quantifiable mIBG uptake in vivo, despite in vitro uptake. 124I-mIBG with microPET/CT provided an accurate three-dimensional tool for estimating the radiation dose that would be delivered with 131I-mIBG therapy. For example, in our model system, we estimated that the administration of 131I-mIBG in the range of 52.8–206 MBq would deliver 20 Gy to tumors.

Conclusions

The overexpression of hNET was found to be critical for 124I-mIBG uptake and retention in vivo. The quantitative 124I-mIBG PET/CT is a promising new tool to predict tumor radiation doses with 131I-mIBG therapy of neuroblastoma. This methodology may be applied to tumor dosimetry of 131I-mIBG therapy in human subjects using 124I-mIBG pretherapy PET/CT data.

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Acknowledgments

This work was supported in part by the V Foundation (K.K.M.), National Cancer Institute under grant K25 CA114254 (Y.S.) and R01 CA154561 (Y.S.), BAERI of KRF funded by MEST grant 2011-0006368 (C.L.L.), National Cancer Institute grant R01 CA102321 (W.A.W.), P01 CA081403 (W.A.W. and K.K.M.), Dougherty Foundation (K.K.M.), and Alex Lemonade Foundation (K.K.M. and W.A.W.).

Conflict of Interest Disclosure

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, 94143, USA

    Youngho Seo, Shorouk F. Dannoon, Stephanie T. Murphy, Henry F. VanBrocklin & Miguel Hernandez-Pampaloni

  2. Department of Radiation Oncology, University of California, San Francisco, CA, 94143, USA

    Youngho Seo & Daphne A. Haas-Kogan

  3. UC Berkeley-UCSF Graduate Program in Bioengineering, University of California, San Francisco, CA, 94143, USA

    Youngho Seo

  4. Department of Pediatrics, University of California, San Francisco, CA, 94143, USA

    W. Clay Gustafson, Erin A. Nekritz, William A. Weiss & Katherine K. Matthay

  5. Department of Radiological Science and Research Institute of Health Science, Yonsei University, Wonju, Korea

    Chang-Lae Lee

  6. Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA

    Daphne A. Haas-Kogan & William A. Weiss

  7. Department of Neurology, University of California, San Francisco, CA, 94143, USA

    William A. Weiss

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  1. Youngho Seo
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Correspondence to Youngho Seo.

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Seo, Y., Gustafson, W.C., Dannoon, S.F. et al. Tumor Dosimetry Using [124I]m-iodobenzylguanidine MicroPET/CT for [131I]m-iodobenzylguanidine Treatment of Neuroblastoma in a Murine Xenograft Model. Mol Imaging Biol 14, 735–742 (2012). https://doi.org/10.1007/s11307-012-0552-4

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