Physical aspects of scintigraphybased dosimetry for nuclear medicine therapy

Summary

In nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism.

This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

Zusammenfassung

Die Anwendung radioaktiv markierter Antikörper bzw. Peptide in der nuklearmedizinischen Therapie ist ein Forschungsgebiet, das zunehmend an Bedeutung gewinnt. Die Dosimetrie soll hierbei die Abschätzung der maximal möglichen Tumordosis ermöglichen unter Berücksichtigung der mit der ionisierenden Strahlung verbundenen Risiken insbesondere für die kritischen Organe. Grundlage derartiger Berechnungen ist die Ermittlung von Daten (z. B. der Biokinetik radioaktiv markierter Substanzen), die über die nuklearmedizinische Bildgebung bestimmt und als Eingangsgrößen für den bekannten MIRD-Formalismus verwendet werden.

In dieser Arbeit werden die Methoden und die Schwierigkeiten beschrieben, die mit der szintigraphischen Bestimmung von Organkinetiken verbunden sind. Die physikalischen Eigenschaften der szintigraphischen Bildgebungsverfahren PET, SPECT und planare Szintigraphie werden in Hinblick auf ihre klinischen Einsatzmöglichkeiten in der Dosimetrie eingehend erörtert. Die Eigenschaften der für Therapie und Dosimetrie verfügbaren Radionuklide werden berücksichtigt. Der Einsatz der planaren Szintigraphie als Methode der Wahl wird in ihren Grenzen dargestellt und diskutiert. Darauf basierend werden Empfehlungen zur Durchführung der Dosimetrie inkorporierter Radionuklide ausgesprochen, welche alle hierzu notwendigen Schritte umfassen, beginnend mit der Datenakquisition über die erforderlichen Korrekturen bis zur Datenauswertung. Hierdurch soll eine verlässliche Abschätzung von Organdosen bei nuklearmedizinischen Therapien gewährleistet werden.

Keywords

Dosimetry - nuclear medicine therapy - scintigraphy

Schlüsselwörter

Dosimetrie - nuklearmedizinische Therapie - Szintigraphie

• References

• 1 Hainsworth JD, Spigel DR, Markus TM. et al. Rituxi- mab plus short-duration chemotherapy followed by yttrium-90 Ibritumomab tiuxetan as first-line treatment for patients with follicular non-Hodgkin lymphoma: a phase II trial of the Sarah Cannon Oncology Research Consortium. Clin Lymphoma Myeloma 2009; 9: 223-228.
• 2 De Jong M, Breeman WA, Kwekkeboom DJ. et al. Tumor imaging and therapy using radiolabeled somatostatin analogues. Acc Chem Res 2009; 42: 873-880.
• 3 De Jong M, Valkema R, Jamar F. et al. Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med 2002; 32: 133-140.
• 4 Kwekkeboom DJ, Krenning EP, Lebtahi R. et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: peptide receptor radionuclide therapy with radiolabeled somatosta- tin analogs. Neuroendocrinology 2009; 90: 220-226.
• 5 Van Essen M, Krenning EP, Kam BL. et al. Peptide- receptor radionuclide therapy for endocrine tumors. Nat Rev Endocrinol 2009; 5: 382-393.
• 6 Morschhauser F, Radford J, Van Hoof A. et al. Phase III trial of consolidation therapy with yttrium- 90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced fol- licular lymphoma. J Clin Oncol 2008; 26: 5156-5164.
• 7 Kwekkeboom DJ, Mueller-Brand J, Paganelli G. et al. Overview of results of peptide receptor radio-nuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med 2005; 46 (Suppl 1) 62S-66S.
• 8 Zoller F, Eisenhut M, Haberkorn U, Mier W. Endo- radiotherapy in cancer treatment – basic concepts and future trends. Eur J Pharmacol 2009; 625: 55-62.
• 9 Otte A, van de Wiele C, Dierckx RA. Radiolabeled immunotherapy in non-Hodgkin's lymphoma treatment: the next step. Nucl Med Commun 2009; 30: 5-15.
• 10 Esser JP, Krenning EP, Teunissen JJ. et al. Comparison of [¹⁷⁷Lu-D0TA(0),Tyr(3)]octreotate and [¹⁷⁷Lu-D0TA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT?. Eur J Nucl Med Mol Imaging 2006; 33: 1346-1351.
• 11 Verordnung über den Schutz vor Schäden durch ionisierende Strahlen (StrlSchV). Bundesgesetzblatt I. 2001: 1714 (2002, 1459).
• 12 Richtlinie nach der Verordnung über den Schutz vor Schäden durch ionisierende Strahlen (StrlSchV) vom 22.04.2002 (Richtlinie Strahlenschutz in der Medizin). Rundschreiben des BMU vom 24.6.2002 – RS II 4 – 11432/1. Verordnung über den Schutz vor Schäden durch ionisierende Strahlen (Strahlenschutzverordnung – StrlSchV). vom 20.07.2001 (BGBI. I S. 1714), zuletzt geändert am 18.06.2002 (BGBI. I S. 1869) BMU 2004
• 13 Thierens HM, Monsieurs MA, Bacher K. Patient dosimetry in radionuclide therapy: the whys and the wherefores. Nucl Med Commun 2005; 26: 593-599.
• 14 Stabin MG. Update: the case for patient-specific dosimetry in radionuclide therapy. Cancer Biother Radiopharm 2008; 23: 273-284.
• 15 Sgouros G, Frey E, Wahl R. et al. Three-dimensional imagingbased radiobiological dosimetry. Semin Nucl Med 2008; 38: 321-334.
• 16 Howell RW, Wessels BW, Loevinger R. et al. The MIRD perspective 1999. Medical Internal Radiation Dose Committee. J Nucl Med 1999; 40: 3S-10S.
• 17 Loevinger R, Budinger TF, Watson EE. MIRD Primer for Absorbed Dose Calculations Revised. New York, NY: Society of Nuclear Medicine; 1991
• 18 Snyder WS, Ford MR, Warner GG, Watson SB. “S,” absorbed dose per unit cumulated activity for selected radionuclides and organs. MIRD Pamphlet No. 11. New York: The Society of Nuclear Medicine; 1975
• 19 Bolch WE, Bouchet LG, Robertson JS. et al. MIRD pamphlet No. 17: the dosimetry of nonuniform activity distributions--radionuclide S values at the voxel level. Medical Internal Radiation Dose Committee. J Nucl Med 1999; 40: 11S-36S.
• 20 Behr TM, Griesinger F, Riggert J. et al. High-dose myeloablative radioimmunotherapy of mantle cell non-Hodgkin lymphoma with the iodine-131-la- beled chimeric anti-CD20 antibody C2B8 and autologous stem cell support. Cancer 2002; 94: 1363-1372.
• 21 Bodei L, Cremonesi M, Zoboli S. et al. Receptor-mediated radionuclide therapy with ⁹⁰Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging 2003; 30: 207-216.
• 22 Wiseman GA, White CA, Stabin M. et al. Phase I/II ⁹⁰Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma. Eur J Nucl Med 2000; 27: 766-777.
• 23 Delaloye AB, Antonescu C, Louton T. et al. Dosimetry of ⁹⁰Yibritumomab tiuxetan as consolidation of first remission in advanced-stage follicular lymphoma: results from the international phase 3 firstline indolent trial. J Nucl Med 2009; 50: 1837-1843.
• 24 Stabin MG. Uncertainties in internal dose calculations for radiopharmaceuticals. J Nucl Med 2008; 49: 853-860.
• 25 Siegel JA, Thomas SR, Stubbs JB. et al. MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates. J Nucl Med 1999; 40: 37S-61S.
• 26 Geworski L, Knoop BO, Munz DL. Bildgebende Messtechnik in der Nuklearmedizin. München: Zuckschwerdt; 2004
• 27 Dillman LT. NM-MIRD pamphlet 6: radionuclide decay schemes and nuclear parameters for use in radiation-dose estimation. 2. J Nucl Med 1970; Suppl 4 7-32.
• 28 Dillman LT. Radionuclide decay schemes and nuclear parameters for use in radiationdose estimation. J Nucl Med 1969; 10 (Suppl 2) 1-32.
• 29 International Commission on Radiological Protection. Radiation dose to patients from radiophar-maceuticals. ICRP Publication. New York: Pergamon Press; 1987
• 30 Cristy M, Eckerman K. Specific Absorbed Fractions of Energy at Various Ages from Internal Photon Sources (I-VII). Oak Ridge National Laboratory Report ORNL/TM-8381/V1-7. Springfield, VA: 1987
• 31 Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys 2003; 85: 294-310.
• 32 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: 1023-1027.
• 33 Glatting G, Landmann M, Kull T. et al. Internal radionuclide therapy: the ULMDOS software for treatment planning. Med Phys 2005; 32: 2399-2405.
• 34 Stabin MG. MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 1996; 37: 538-546.
• 35 Herzog H, Tellmann L, Scholten B. et al. PET imaging problems with the non-standard positron emitters yttrium-86 and iodine-124. Q J Nucl Med Mol Imaging 2008; 52: 159-165.
• 36 Kull T, Ruckgaber J, Weller R. et al. Quantitative imaging of yttrium-86 PET with the ECAT EXACT HR+ in 2D mode. Cancer Biother Radiopharm 2004; 19: 482-490.
• 37 Vandenberghe S. Three-dimensional positron emission tomography imaging with ¹²⁴I and ⁸⁶Y. Nucl Med Commun 2006; 27: 237-245.
• 38 Laforest R, Liu X. Image quality with non-standard nuclides in PET. Q J Nucl Med Mol Imaging 2008; 52: 151-158.
• 39 Buchholz HG, Herzog H, Forster GJ. et al. PET imaging with yttrium-86: comparison of phantom measurements acquired with different PET scanners before and after applying background subtraction. Eur J Nucl Med Mol Imaging 2003; 30: 716-720.
• 40 Pentlow KS, Finn RD, Larson SM. et al. Quantitative imaging of yttrium-86 with PET. The occurrence and correction of anomalous apparent activity in high density regions. Clin Positron Imaging 2000; 3: 85-90.
• 41 Beattie BJ, Finn RD, Rowland DJ, Pentlow KS. Quantitative imaging of bromine-76 and yttrium-86 with PET: a method for the removal of spurious activity introduced by cascade gamma rays. Med Phys 2003; 30: 2410-2423.
• 42 Walrand S, Jamar F, Mathieu I. et al. Quantitation in PET using isotopes emitting prompt single gammas: application to yttrium-86. Eur J Nucl Med Mol Imaging 2003; 30: 354-361.
• 43 Jamar F, Barone R, Mathieu I. et al. ⁸⁶Y-DOTA0)- D-Phe1-Tyr3-octreotide (SMT487) – a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging 2003; 30: 510-518.
• 44 Pauwels S, Barone R, Walrand S. et al. Practical dosi- metry of peptide receptor radionuclide therapy with ⁹⁰Y-labeled somatostatin analogs. J Nucl Med 2005; 46 (Suppl 1) 92S-98S.
• 45 Freudenberg LS, Jentzen W, Gorges R. et al. ¹²⁴I-PET dosimetry in advanced differentiated thyroid cancer: therapeutic impact. Nuklearmedizin 2007; 46: 121-128.
• 46 Jentzen W, Weise R, Kupferschlager J. et al. Iod- ine-124 PET dosimetry in differentiated thyroid cancer: recovery coefficient in 2D and 3D modes for PET(/CT) systems. Eur J Nucl Med Mol Imaging 2008; 35: 611-623.
• 47 Sgouros G, Kolbert KS, Sheikh A. et al. Patient-specific dosimetry for 131I thyroid cancer therapy using ¹²⁴I PET and 3-dimensional-internal dosimetry (3D-ID) software. J Nucl Med 2004; 45: 1366-1372.
• 48 Jentzen W, Hobbs RF, Stahl A. et al. Pre-therapeutic ¹²⁴I PET(/CT) dosimetry confirms low average absorbed doses per administered 131I activity to the salivary glands in radioiodine therapy of differentiated thyroid cancer. Eur J Nucl Med Mol Imaging 2010; 37: 884-895.
• 49 Pettinato C, Sarnelli A, Di Donna M. et al. 68Ga- DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors. Eur J Nucl Med Mol Imaging 2008; 35: 72-79.
• 50 Hartmann H, Zöphel K, Freudenberg R. et al. Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations. Nuklearmedizin 2009; 48: 201-207.
• 51 He B, Frey EC. Comparison of conventional, model-based quantitative planar, and quantitative SPECT image processing methods for organ activity estimation using 111In agents. Phys Med Biol 2006; 51: 3967-3981.
• 52 Assie K, Dieudonne A, Gardin I. et al. Comparison between 2D and 3D dosimetry protocols in ⁹⁰Y-ibri- tumomab tiuxetan radioimmunotherapy of patients with non-Hodgkin's lymphoma. Cancer Biother Radiopharm 2008; 23: 53-64.
• 53 Schaefer A, Schweizer B, Georgi JC. et al. Voxel-basierte Ermittlung von Organ- und Herddosen vor und unter interner Radionuklid-Therapie: Erste klinische Erfahrungen mit dem Dosimetrie-Programm STRATOS. Nuklearmedizin. 2009 48. A 48.
• 54 Hudson HM, Larkin RS. Accelerated image reconstruction using ordered subsets of projection data. IEEE Trans Med Imaging 1994; 13: 601-609.
• 55 He B, Du Y, Song X. et al. A Monte Carlo and physical phantom evaluation of quantitative 111In- SPECT. Phys Med Biol 2005; 50: 4169-4185.
• 56 He B, Wahl RL, Du Y, et al. Comparison of residence time estimation methods for radioimmunotherapy dosimetry and treatment planning – Monte Carlo simulation studies. IEEE Trans Med Imaging 2008; 27: 521-530.
• 57 Flux G, Bardies M, Monsieurs M. et al. The impact of PET and SPECT on dosimetry for targeted radionuclide therapy. Z Med Phys 2006; 16: 47-59.
• 58 Sandstrom M, Garske U, Granberg D. et al. Individualized dosimetry in patients undergoing therapy with ¹⁷⁷Lu-DOTA-D-Phe (1)-Tyr (3)-octreotate. Eur J Nucl Med Mol Imaging 2009; 37: 212-225.
• 59 He B, Frey EC, Tsui BM. Comparison and validation of conjugate view planar, model-based quantitative planar, and quantitative SPECT methods for whole organ activity estimation. J Nucl Med 2005; 46: 50P.
• 60 International Electro technical Commission. IEC 61675-2: Radionuclide imaging devices – Characteristics and test conditions- Part 2: Single photon emission computed tomographs. Geneva: International Electrotechnical Commission; 1998
• 61 Zander A, Winter C, Schaefer A. et al. Penetrationsanteil der für mIn-Dosimetrie verwendeten Kollimatoren. Nuklearmedizin 2007; 46: P53.
• 62 Ogawa K, Harata Y, Ichihara T. et al. A practical method for position-dependent Compton-scatter correction in single photon emission CT. IEEE Trans Med Imaging 1991; 10: 408-412.
• 63 Wiseman GA, Leigh B, Erwin WD. et al. Radiation dosimetry results for Zevalin radioimmunotherapy of rituximab-refractory non-Hodgkin lymphoma. Cancer 2002; 94 (4 Suppl) 1349-1357.
• 64 Thomas SR, Stabin MG, Chen CT, Samaratunga RC. MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose calculations. Task Group of the MIRD Committee, Society of Nuclear Medicine. J Nucl Med 1999; 40: 102S-123S.
• 65 Jaszczak RJ, Greer KL, Floyd Jr CE. et al. Improved SPECT quantification using compensation for scattered photons. J Nucl Med 1984; 25: 893-900.
• 66 Berberich R, Brill G, Schmidt EL. Verbesserung des Auflösungsvermögens der Gammakamera durch gewichtete Subtraktion der Streustrahlung. Nuc- Compact 1984; 15: 5.
• 67 King MA, Hademenos GJ, Glick SJ. A dual-photo- peak window method for scatter correction. J Nucl Med 1992; 33: 605-612.
• 68 Koral KF, Swailem FM, Buchbinder S. et al. SPECT dual-energy-window Compton correction: scatter multiplier required for quantification. J Nucl Med 1990; 31: 90-98.
• 69 Larsson SA. Gamma camera emission tomography. Development and properties of a multi-sectional emission computed tomography system. Acta Radiol Suppl 1980; 363: 1-75.
• 70 Heidenreich R, Zander A, Knoop BO, Geworski L. Grenzen der Anwendbarkeit geometrischer Mittelwertbildung in der Dosimetrie für die Absorptionskorrektur. Nuklearmedizin 2007; 46: P47.
• 71 Sorensen JA. Method for quantitative measurements of radioactivity in vivo by wholebody counting. In: Hine GJ, Sorensen JA. (eds) Instrumentation in nuclear medicine. Vol 2. New York: Academic Press; 1974: 311-348.
• 72 Jordan K, Knoop B. Meßtechnik in der EmissionsComputertomographie. In: Diethelm L, Heuck F, Olsson O. et al. (eds) Handbuch der medizinischen Radiologie. Vol Bd XV/1B Berlin: Springer; 1988: 281-282.
• 73 Myers MJ, Lavender JP, de Oliveira JB, Maseri A. A simplified method of quantitating organ uptake using a gamma camera. Br J Radiol 1981; 54: 1062-1067.
• 74 Stabin MG. Fundamentals of Nuclear Medicine Dosimetry. New York: Springer; 2008
• 75 Glatting G, Kull T, Blumstein NM. et al. Dosimetry with 188Re-labelled monoclonal anti-CD66 antibodies. A simplified approach based on a single measurement 3 h p.i. Nuklearmedizin 2006; 45: 134-138.
• 76 International Commission on Radiological Protection. 1990 Recommendations of the International Commission on Radiological Protection. ICRP Publication 60 ed. New York: Pergamon Press; 1991
• 77 Dale R, Carabe-Fernandez A. The radiobiology of conventional radiotherapy and its application to radionuclide therapy. Cancer Biother Radiopharm 2005; 20: 47-51.
• 78 Dale R. The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. Br J Radiol 1985; 58: 515-528.
• 79 Sgouros G, Stabin M, Erdi Y. et al. Red marrow dosimetry for radiolabeled antibodies that bind to marrow, bone, or blood components. Med Phys 2000; 27: 2150-2164.
• 80 Cristy M. Active bone marrow distribution as a function of age in humans. Phys Med Biol 1981; 26: 389-400.
• 81 Sgouros G. Bone marrow dosimetry for radio- immunotherapy: theoretical considerations. J Nucl Med 1993; 34: 689-694.
• 82 Siegel JA, Lee RE, Pawlyk DA. et al. Sacral scinti- graphy for bone marrow dosimetry in radioimmunotherapy. Int J Rad Appl Instrum B 1989; 16: 553-559.
• 83 Hindorf C, Linden O, Tennvall J. et al. Evaluation of methods for red marrow dosimetry based on patients undergoing radioimmunotherapy. Acta Oncol 2005; 44: 579-588.
• 84 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.
• 85 Hindorf C, Glatting G, Chiesa C. et al. Guidelines for Bone Marrow and Whole Body Dosimetry. Eur J Nucl Med Mol Imaging. 2010 in press.