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Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent

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

Abstract

Purpose

Prostate-specific membrane antigen (PSMA), a type-II integral membrane protein highly expressed in prostate cancer, has been extensively used as a target for imaging and therapy. Among the available PET radiotracers, the low molecular weight agents that bind to PSMA are proving particularly effective. We present the dosimetry results for 18F-DCFPyL in nine patients with metastatic prostate cancer.

Methods

Nine patients were imaged using sequential PET/CT scans at approximately 1, 12, 35 and 70 min, and a final PET/CT scan at approximately 120 min after intravenous administration of 321 ± 8 MBq (8.7 ± 0.2 mCi) of18F-DCFPyL. Time-integrated-activity coefficients were calculated and used as input in OLINDA/EXM software to obtain dose estimates for the majority of the major organs. The absorbed doses (AD) to the eye lens and lacrimal glands were calculated using Monte-Carlo models based on idealized anatomy combined with patient-specific volumes and activity from the PET/CT scans. Monte-Carlo based models were also developed for calculation of the dose to two major salivary glands (parotid and submandibular) using CT-based patient-specific gland volumes.

Results

The highest calculated mean AD per unit administered activity of 18F was found in the lacrimal glands, followed by the submandibular glands, kidneys, urinary bladder wall, and parotid glands. The S-values for the lacrimal glands to the eye lens (0.42 mGy/MBq h), the tear film to the eye lens (1.78 mGy/MBq h) and the lacrimal gland self-dose (574.10 mGy/MBq h) were calculated. Average S-values for the salivary glands were 3.58 mGy/MBq h for the parotid self-dose and 6.78 mGy/MBq h for the submandibular self-dose. The resultant mean effective dose of 18F-DCFPyL was 0.017 ± 0.002 mSv/MBq.

Conclusions

18F-DCFPyL dosimetry in nine patients was obtained using novel models for the lacrimal and salivary glands, two organs with potentially dose-limiting uptake for therapy and diagnosis which lacked pre-existing models.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7–30.

    Article  PubMed  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.

    Article  CAS  PubMed  Google Scholar 

  3. Scher HI, Halabi S, Tannock I, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26:1148–59.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hofer C, Laubenbacher C, Block T, Breul J, Hartung R, Schwaiger M. Fluorine-18-fluorodeoxyglucose positron emission tomography is useless for the detection of local recurrence after radical prostatectomy. Eur Urol. 1999;36:31–5.

    Article  CAS  PubMed  Google Scholar 

  5. Nuñez R, Macapinlac HA, Yeung HW, et al. Combined 18F-FDG and 11C-methionine PET scans in patients with newly progressive metastatic prostate cancer. J Nucl Med. 2002;43:46–55.

    PubMed  Google Scholar 

  6. Shreve PD, Grossman HB, Gross MD, Wahl RL. Metastatic prostate cancer: initial findings of PET with 2-deoxy-2-[F-18]fluoro-D-glucose. Radiology. 1996;199:751–6.

    Article  CAS  PubMed  Google Scholar 

  7. Rowe SP, Gorin MA, Allaf ME, et al. PET imaging of prostate-specific membrane antigen in prostate cancer: current state of the art and future challenges. Prostate Cancer Prostatic Dis. 2016;19:223–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hricak H, Choyke PL, Eberhardt SC, Leibel SA, Scardino PT. Imaging prostate cancer: a multidisciplinary perspective. Radiology. 2007;243:28–53.

    Article  PubMed  Google Scholar 

  9. Lawrentschuk N, Davis ID, Bolton DM, Scott AM. Positron emission tomography and molecular imaging of the prostate: an update. BJU Int. 2006;97:923–31.

    Article  CAS  PubMed  Google Scholar 

  10. De Jong I, Pruim J, Elsinga P, Vaalburg W, Mensink H. 11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer. Eur Urol. 2003;44:32–9.

    Article  PubMed  Google Scholar 

  11. Picchio M, Messa C, Landoni C, et al. Value of [11C] choline-positron emission tomography for re-staging prostate cancer: a comparison with [18F] fluorodeoxyglucose-positron emission tomography. J Urol. 2003;169:1337–40.

    Article  CAS  PubMed  Google Scholar 

  12. Greco C, Cascini G, Tamburrini O. Is there a role for positron emission tomography imaging in the early evaluation of prostate cancer relapse? Prostate Cancer Prostatic Dis. 2008;11:121–8.

    Article  CAS  PubMed  Google Scholar 

  13. Rahmim A, Zaidi H. PET versus SPECT: strengths, limitations and challenges. Nucl Med Commun. 2008;29:193–207.

    Article  PubMed  Google Scholar 

  14. Scattoni V, Picchio M, Suardi N, et al. Detection of lymph-node metastases with integrated [11 C] choline PET/CT in patients with PSA failure after radical retropubic prostatectomy: results confirmed by open pelvic-retroperitoneal lymphadenectomy. Eur Urol. 2007;52:423–9.

    Article  PubMed  Google Scholar 

  15. Schuster DM, Nanni C, Fanti S. PET tracers beyond FDG in prostate cancer. Semin Nucl Med. 2016;46:507–21.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Pandit-Taskar N, O’Donoghue JA, Durack JC, et al. A phase I/II study for analytic validation of 89Zr-J591 immunoPET as a molecular imaging agent for metastatic prostate cancer. Clin Cancer Res. 2015;21:5277–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen Y, Pullambhatla M, Foss CA, et al. 2-(3-{1-Carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid, [18F]DCFPyL, a PSMA-based PET imaging agent for prostate cancer. Clin Cancer Res. 2011;17:7645–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Cho SY, Gage KL, Mease RC, et al. Biodistribution, tumor detection, and radiation dosimetry of 18F-DCFBC, a low-molecular-weight inhibitor of prostate-specific membrane antigen, in patients with metastatic prostate cancer. J Nucl Med. 2012;53:1883–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Szabo Z, Mena E, Rowe SP, et al. Initial evaluation of [(18)F]DCFPyL for prostate-specific membrane antigen (PSMA)-targeted PET imaging of prostate cancer. Mol Imaging Biol. 2015;17:565–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Evangelista L, Briganti A, Fanti S, et al. New clinical indications for 18F/11C-choline, new tracers for positron emission tomography and a promising hybrid device for prostate cancer staging: a systematic review of the literature. Eur Urol. 2016;70:161–75.

    Article  PubMed  Google Scholar 

  21. Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005;46:1023–7.

    PubMed  Google Scholar 

  22. Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD pamphlet no. 21: a generalized schema for radiopharmaceutical dosimetry – standardization of nomenclature. J Nucl Med. 2009;50:477–84.

    Article  CAS  PubMed  Google Scholar 

  23. Plyku D, Hobbs RF, Huang K, et al. Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in 124I-PET/CT based dosimetry for 131I therapy of metastatic differentiated thyroid cancer. J Nucl Med. 2017;58:1146–54.

    Article  PubMed  PubMed Central  Google Scholar 

  24. ICRP. Basic anatomical and physiological data for use in radiological protection: reference values. A report of age- and gender-related differences in the anatomical and physiological characteristics of reference individuals. ICRP Publication 89. Ann ICRP. 2002;32:5–265.

    Article  Google Scholar 

  25. SAAM II User Guide. Seattle: SAAM Institute, University of Washington; 1997.

  26. Snyder WS, Cook MJ, Nasset ES, Karhausen LR, Howells GP, Tipton IH. Report of the task group on reference man. ICRP publication 23. Elmsford, NY: International Commission on Radiological Protection; 1975.

    Google Scholar 

  27. ICRP. 1990 Recommendations of the International Commission on Radiological Protection. ICRP publication 60. Ann ICRP. 1991;21(1-3)

  28. Thomas SR, Stabin MG, Chen CT, Samaratunga RC. MIRD Pamphlet No. 14: a dynamic urinary bladder model for radiation dose calculations. J Nucl Med. 2012;33:783–802.

  29. Agostinelli S, Allison J, Amako KA, et al. GEANT4 – a simulation toolkit. Nucl Instrum Methods Phys Res A. 2003;506:250–303.

    Article  CAS  Google Scholar 

  30. Tamboli DA, Harris MA, Hogg JP, Realini T, Sivak-Callcott JA. Computed tomography dimensions of the lacrimal gland in normal Caucasian orbits. Ophthalmic Plast Reconstr Surg. 2011;27:453–6.

    Article  Google Scholar 

  31. Price KM, Richard MJ. Ophthalmic Pearls: The tearing patient: diagnosis and management. EyeNet Magazine, 2009; p. 33–5.

  32. Montés-Micó R. Role of the tear film in the optical quality of the human eye. J Cataract Refract Surg. 2007;33:1631–5.

    Article  PubMed  Google Scholar 

  33. Sgouros G, Frey E, Wahl R, He B, Prideaux A, Hobbs R. Three-dimensional imaging-based radiobiological dosimetry. Semin Nucl Med. 2008;38:321–34.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Prideaux AR, Song H, Hobbs RF, et al. Three-dimensional radiobiologic dosimetry: application of radiobiologic modeling to patient-specific 3-dimensional imaging-based internal dosimetry. J Nucl Med. 2007;48:1008–16.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sgouros G, Hobbs RF, Atkins FB, Van Nostrand D, Ladenson PW, Wahl RL. Three-dimensional radiobiological dosimetry (3D-RD) with 124I PET for 131I therapy of thyroid cancer. Eur J Nucl Med Mol Imaging. 2011;38(Suppl 1):S41–7.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Hobbs RF, Wahl RL, Lodge MA, et al. 124I PET-Based 3D-RD dosimetry for a pediatric thyroid cancer patient: real time treatment planning and methodologic comparison. J Nucl Med. 2009; 50(11):1844–47.

    Article  PubMed  PubMed Central  Google Scholar 

  37. King-Smith PE, Fink BA, Hill RM, Koelling KW, Tiffany JM. The thickness of the tear film. Curr Eye Res. 2004;29:357–68.

    Article  PubMed  Google Scholar 

  38. Pfob CH, Ziegler S, Graner FP, et al. Biodistribution and radiation dosimetry of 68Ga-PSMA HBED CC – a PSMA specific probe for PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging. 2016;43:1962–70.

    Article  CAS  PubMed  Google Scholar 

  39. Herrmann K, Bluemel C, Weineisen M, et al. Biodistribution and radiation dosimetry for a probe targeting prostate-specific membrane antigen for imaging and therapy. J Nucl Med. 2015;56:855–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Afshar-Oromieh A, Hetzheim H, Kratochwil C, et al. The theranostic PSMA ligand PSMA-617 in the diagnosis of prostate cancer by PET/CT: biodistribution in humans, radiation dosimetry, and first evaluation of tumor lesions. J Nucl Med. 2015;56:1697–705.

    Article  CAS  PubMed  Google Scholar 

  41. Okamoto S, Thieme A, Allmann J, et al. Radiation dosimetry for 177Lu-PSMA I&T in metastatic castration-resistant prostate cancer: absorbed dose in normal organs and tumor lesions. J Nucl Med. 2017;58:445–50.

    Article  CAS  PubMed  Google Scholar 

  42. Hohberg M, Eschner W, Schmidt M, et al. Lacrimal glands may represent organs at risk for radionuclide therapy of prostate cancer with [(177)Lu]DKFZ-PSMA-617. Mol Imaging Biol. 2016;18:437–45.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge the support of the Prostate Cancer Foundation – Young Investigator Award, the Patrick C. Walsh Prostate Cancer Research Fund, EB006351, CA134675, CA184228, CA103175, CA183031 and CA116477.

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Authors and Affiliations

  1. The Russell H. Morgan Department of Radiology and Radiological Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Donika Plyku, Esther Mena, Steven P. Rowe, Martin A. Lodge, Zsolt Szabo, Steve Y. Cho, Martin G. Pomper, George Sgouros & Robert F. Hobbs

  2. Department of Radiology, School of Medicine and Public Health, University of Wisconsin, CRB II 4M.60, 1550 Orleans St., Baltimore, MD, 21287, USA

    Steve Y. Cho

  3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Martin G. Pomper

  4. Department of Radiation Oncology, School of Medicine, Johns Hopkins University, CRB II 4M.60, 1550 Orleans St., Baltimore, MD, USA

    George Sgouros & Robert F. Hobbs

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  1. Donika Plyku
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Correspondence to Robert F. Hobbs.

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Plyku, D., Mena, E., Rowe, S.P. et al. Combined model-based and patient-specific dosimetry for 18F-DCFPyL, a PSMA-targeted PET agent. Eur J Nucl Med Mol Imaging 45, 989–998 (2018). https://doi.org/10.1007/s00259-018-3939-x

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  • DOI: https://doi.org/10.1007/s00259-018-3939-x

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