Radiation exposure of patients during ⁶⁸Ga-DOTATOC PET/CT examinations

Summary

Aim: Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOCfor patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. Patients, methods: Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112 ± 22) MBq ⁶⁸Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i. Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/ EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). Results: Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. Conclusion: ⁶⁸Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose).

Zusammenfassung

Ziel: Untersuchung der Biodistribution und Ermittlung von dosimetrischen Daten für ⁶⁸Ga- DOTATOC bei Patienten im Rahmen der Krankenversorgung zum Nachweis oder Ausschluss von neuroendokrinen Tumoren. Patienten, Methoden: Bei 14 Patienten (8 Männer, 6 Frauen) konnten nach Injektion von (112 ± 22)MBq ⁶⁸Ga-DOTATOC dynamische Messungen am PET/CT (Biograph 16) über 20 min gefolgt von statischen Ganzkörper- Aufnahmen über 8 Bettpositionen in 3D-Technik 30 min p.i. und 120 min p.i. ausgewertet werden. Die Urinausscheidung wurde gemessen, die Blutaktivität wurde bildgebend nichtinvasiv aus dem Blutpool des Herzen ermittelt. Die für die Dosimetrie relevanten Organe waren Milz, Niere, Leber, Nebenniere, Harnblase und Hypophyse. Dosimetrische Werte wurden mit der OLINDA/ EXM 1.0 Software errechnet und spezifische Organanreicherungen auch als standardisierte Uptake-Werte (SUV) angegeben. Ergebnisse: Eine schnelle physiologische Aufnahme des Radiotracers erfolgte in Leber, Milz, Nieren, Nebennieren und Hypophyse, die mittleren SUV-Werte betrugen 6, 20, 16, 10 und 4. Die Elimination erfolgte ausschließlich renal in die Harnblase (16% der injizierten Aktivität innerhalb von 2 h). Eine Umverteilung konnte nicht beobachtet werden. Die Organe mit der höchsten Strahlenexposition waren die Milz (0,24 mSv/MBq) und die Nieren (0,22 mSv/MBq), die über die Geschlechter gemittelte effektive Dosis betrug 0,023 mSv/MBq. Schlussfolgerung: ⁶⁸Ga-DOTATOC wird bereits umfangreich zur Diagnostik somatostatinrezeptor-positiver Tumore eingesetzt, weil es gegenüber 111In-Somatostatin derivaten wesentliche Vorteile aufweist. Die jetzt ermittelten dosimetrischen Werte sind niedriger als die Dosis von 111In-OctreoScan. Die Strahlenexposition der CT zur Schwächungskorrektur der PET-Daten beträgt 1 mSv (Niedrigdosis).

Keywords

⁶⁸Ga-DOTATOC - somatostatinreceptor - radiation exposure - dosimetry - PET - PET/CT

Schlüsselwörter

⁶⁸Ga-DOTATOC - Somatostatinrezeptor - Strahlen exposition - Dosimetrie - PET - PET/CT

• Literatur

• 1 Antunes P, Ginj M, Zhang H. et al. Are radiogalliumlabelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?. Eur J Nucl Med Mol Imaging 2007; 34: 982-993.
• 2 Balon HR, Goldsmith SJ, Siegel BA. et al. Procedure guideline for somatostatin receptor scintigraphy with 111In-pentetreotide. J Nucl Med 2001; 42: 1134-1138.
• 3 Bernhardt P, Ahlman H, Nilsson O. et al. Evaluation of 111In labeled somatostatin analogs for targeted therapy of somatostatin receptor positive tumors. Cancer Biother Radiopharm 2003; 18: 249-252.
• 4 Beyer T, Antoch G, Muller S. et al. Acquisition protocol considerations for combined PET/CT imaging. J Nucl Med 2004; 45 (Suppl 1) 25S-35S.
• 5 Bombardieri E, Aktolun C, Baum RP. et al. mIn-pentetreotide scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging 2003; 30: BP140-147.
• 6 Bouchet LG, Bolch WE, Blanco HP. et al. MIRD Pamphlet No 19: absorbed fractions and radio- nuclide S values for six age-dependent multiregion models of the kidney. J Nucl Med 2003; 44: 1113-1147.
• 7 Brix G, Baum RP, Lechel U, Noßke D. Strahlenexposition von Patienten bei der Rezeptor-PET/ CT mit dem ⁶⁸Ga-markierten Somatostatinanalogon DOTA-NOC. Nuklearmedizin 2006; 45: A101.
• 8 Buchmann I, Henze M, Engelbrecht S. et al. Comparison of ⁶⁸Ga-DOTATOC PET and 111In- DTPAOC (Octreoscan) SPECT in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2007; 34: 1617-1626.
• 9 Cremonesi M, Ferrari M, Bodei L. et al. Dosimetry in Peptide radionuclide receptor therapy: a review. J Nucl Med 2006; 47: 1467-1475.
• 10 Forrer F, Uusijarvi H, Waldherr C. et al. A comparison of 111In-DOTATOC and 111In-DOTATATE: biodistribution and dosimetry in the same patients with metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004; 31: 1257-1262.
• 11 Gabriel M, Decristoforo C, Kendler D. et al. ⁶⁸Ga- DOTA-Tyr3-octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007; 48: 508-518.
• 12 Hartmann H, Wunderlich G, Zöphel K. et al. Strahlenexposition von Patienten bei Untersuchungen mit ⁶⁸Ga-DOTATOC am PET/CT. Nuklearmedizin 2008; 47: A105.
• 13 Hays MT, Watson EE, Thomas SR, Stabin M. MIRD dose estimate report no. 19: radiation absorbed dose estimates from ¹⁸F-FDG. J Nucl Med 2002; 43: 210-214.
• 14 Henze M, Dimitrakopoulou-Strauss A, Milker Zabel S. et al. Characterization of ⁶⁸Ga-DOTA- D-Phe1-Tyr3-octreotide kinetics in patients with meningiomas. J Nucl Med 2005; 46: 763-769.
• 15 Henze M, Schuhmacher J, Hipp P. et al. PET imaging of somatostatin receptors using ⁶⁸Ga-DOTA- D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med 2001; 42: 1053-1056.
• 16 Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem 2000; 7: 971-994.
• 17 Hietschold V, Koch A, Laniado M, Abolmaali ND. Computed tomography: influence of varying tube current on patient dose and correctness of effective dose calculations. Rofo 2008; 180: 430-439.
• 18 Hofmann M, Maecke H, Borner R. et al. Biokinetics and imaging with the somatostatin receptor PET radioligand ⁶⁸Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001; 28: 1751-1757.
• 19 Koukouraki S, Strauss LG, Georgoulias V. et al. Evaluation of the pharmacokinetics of ⁶⁸Ga- DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging 2006; 33: 460-466.
• 20 Kowalski J, Henze M, Schuhmacher J. et al. Evaluation of positron emission tomography imaging using ⁶⁸Ga-DOTA-D Phe(1)-Tyr(3)-Octreotide in comparison to 111In-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol 2003; 5: 42-48.
• 21 Kwekkeboom DJ, Kooij PP, Bakker WH. et al. Comparison of 111In-DOTA-Tyr3-octreotide and 111In- DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med 1999; 40: 762-767.
• 22 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.
• 23 Pacak K, Eisenhofer G, Goldstein DS. Functional imaging of endocrine tumors: role of positron emission tomography. Endocr Rev 2004; 25: 568-580.
• 24 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.
• 25 Reilly RM, Chen P, Wang J. et al. Preclinical pharmacokinetic, biodistribution, toxicology, and dosi- metry studies of 111In-DTPA-human epidermal growth factor: an auger electron-emitting radio- therapeutic agent for epidermal growth factor receptor-positive breast cancer. J Nucl Med 2006; 47: 1023-1031.
• 26 Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med 2006; 36: 228-247.
• 27 Sgouros G, Frey E, Wahl R. et al. Three-dimensional imaging-based radiobiological dosimetry. Semin Nucl Med 2008; 38: 321-334.
• 28 Stabin MG, Kooij PP, Bakker WH. et al. Radiation dosimetry for indium-111-pentetreotide. J Nucl Med 1997; 38: 1919-1922.
• 29 Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys 2003; 85: 294-310.
• 30 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.
• 31 Williams LE, Liu A, Yamauchi DM. et al. The two types of correction of absorbed dose estimates for internal emitters. Cancer 2002; 94: 1231-1234.
• 32 Zhernosekov KP, Filosofov DV, Baum RP. et al. Processing of generator-produced ⁶⁸Ga for medical application. J Nucl Med 2007; 48: 1741-1748.
• 33 Zöphel K, Strumpf A, Wunderlich G. et al. Cure of neuroendocrine carcinoma by peptide receptor radio- nuclide therapy. Clin Nucl Med 2008; 33: 690-691.