Abstract
Objectives
The aim of this work was the evaluation of biodistribution and radiation dosimetry of 68Ga-DOTANOC in patients affected by neuroendocrine tumors.
Materials and methods
We enrolled nine patients (six male and three female) affected by different types of neuroendocrine tumors (NETs). Each patient underwent four whole body positron emission tomography (PET) scans, respectively, at 5, 20, 60, and 120 min after the intravenous injection of about 185 MBq of 68Ga-DOTANOC. Blood and urine samples were taken at different time points post injection: respectively, at about 5, 18, 40, 60, and 120 min for blood and every 40–50 min from injection time up to 4 h for urine. The organs involved in the dosimetric evaluations were liver, heart, spleen, kidneys, lungs, pituitary gland, and urinary bladder. Dosimetric evaluations were done using the OLINDA/EXM 1.0 software.
Results
A physiological uptake of 68Ga-DOTANOC was seen in all patients in the pituitary gland, the spleen, the liver, and the urinary tract (kidneys and urinary bladder). Organs with the highest absorbed doses were kidneys \( \left( {{{9.0{\text{E}} - 02 \pm 3.2{\text{E}} - 02{\text{mSv}}} \mathord{\left/ {\vphantom {{9.0{\text{E}} - 02 \pm 3.2{\text{E}} - 02{\text{mSv}}} {{\text{MBq}}}}} \right. \kern-\nulldelimiterspace} {{\text{MBq}}}}} \right) \). The mean effective dose equivalent (EDE) was \( {{2.5{\text{E}} - 02 \pm 4.6{\text{E}} - 03{\text{mSv}}} \mathord{\left/ {\vphantom {{2.5{\text{E}} - 02 \pm 4.6{\text{E}} - 03{\text{mSv}}} {{\text{MBq}}}}} \right. \kern-\nulldelimiterspace} {{\text{MBq}}}} \).
Discussion and conclusions
The excretion of the compound was principally via urine, giving dose to the kidney and the urinary bladder wall. As SSTR2 is the most frequently expressed somatostatin receptor and 68Ga-DOTANOC has high affinity to it, this compound might play an important role in PET oncology in the future. The dosimetric evaluation carried out by our team demonstrated that 68Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds.
Similar content being viewed by others
References
Maecke HR, Hofmann M, Haberkorn U. 68Ga-labeled peptides in tumor imaging. J Nucl Med 2005;46 suppl.1:172S–8S.
Rufini V, Calcagni ML, Baum RP. Imaging of neuroendocrine tumors. Semin Nucl Med 2006;36:228–47.
Behr TM, Gotthardt M, Barth A, Behe M. Imaging tumors with peptide-based radioligands. Q J Nucl Med 2001;45:189–200.
Kwekkeboom DJ, Krenning EP, de Jong M. Peptide receptor imaging and therapy. J Nucl Med 2000;41:1704–13.
Breeman WA, de Jong M, Kwekkeboom DJ, Valkema R, Bakker WH, Kooij PP, et al. Somatostatin receptormediated imaging and therapy: basic science, current knowledge, limitations and future perspectives. Eur J Nucl Med 2001;28:1421–9.
Gabriel M, Decristoforo C, Kendler D, Dobrozemsky G, Heute D, Uprimny C, et al. 68Ga-DOTA-Tyr3-Octreotide PET in neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and CT. J Nucl Med 2007;48:508–18.
Forster GJ, Engelbach M, Brockmann JJ, Reber HJ, Buchholz HG, Macke HR, et al. Preliminary data on biodistribution and dosimetry for therapy planning of somatostatin receptor positive tumors: comparison of 86Y-DOTATOC and 111In-DTPA-octreotide. Eur J Nucl Med 2001;28:1743–50.
Cremonesi M, Ferrari M, Bodei L, Tosi G, Paganelli G. Dosimetry in peptide radionuclide receptors therapy: a review. J Nucl Med 2006;47:1467–75.
Cremonesi M, Ferrari M, Zoboli S, Chinol M, Stabin MG, Orsi F, et al. Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC. Eur J Nucl Med 1999;26:877–86.
Kowalski J, Henze M, Schuhmacher J, Macke HR, Hofmann M, Haberkorn U. Evaluation of positron emission tomography imaging using [68Ga]-DOTA-DPhe1-Tyr3-Octreotide in comparison to [111In]-DTPAOC SPECT. First results in patients with neuroendocrine tumors. Mol Imaging Biol 2003;5:42–8.
Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher, Strauss LG, Doll J, et al. Characterization of 68Ga-DOTA-D-Phe1-Tyr3-Octreotide kinetics in patients with meningiomas. J Nucl Med 2005;46:763–9.
Hofmann M, Maecke H, Borner R, Weckesser E, Schoffski P, Oei L, et al. Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001;28:1751–7.
Henze M, Schumacher T, Hipp P, Kowalski J, Becker DW, Doll J, et al. PET imaging of somatostatin receptors using [68Ga]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. J Nucl Med 2001;42:1053–6.
Wild D, Schmitt JS, Ginj M, Macke HR, Bernard BF, Krenning E, et al. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labelling with various radiometals. Eur J Nucl Med Mol Imaging 2003;30:1338–47.
Wild D, Macke HR, Waser B, Reubi JC, Ginj M, Rasch H, et al. 68Ga-DOTANOC: a first compound for PET imaging with high affinity for somatostatin receptor subtypes 2 and 5. Eur J Nucl Med Mol Imaging 2005;724.
Baum R, Niesen A, Leonhardi J, Wortmann R, Mueller D, Roesch F. Receptor PET/CT imaging of neuroendocrine tumors using the Ga-68 labelled, high affinity somatostatin analogue DOTA-1-Nal3 octreotide (DOTA-NOC): clinical results in 327 patients. Eur J Nucl Med Mol Imaging 2005;32 Suppl 1:S54–5.
Roesch F, Zhernosekov K, Filosofov D, Jahn M, Jennewein M, Baum R, et al. Processing of Ge-68/Ga-68 generator eluates for labeling of biomolecules via bifunctional chelators. J Nucl Med 2006;47 Suppl 1:162P.
Schuhmacher J, Maier-Borst W. A new 68Ge/68Ga radioisotope generator system for production of 68Ga in dilute HCl. Int J Appl Radiat Isot 1981;32:31–6.
Breeman WA, de Jong M, de Blais E, Bernard BF, Konjinemberg M, Krenning EP. Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med Mol Imaging 2005;32:478–85.
Schmidtlein CR, Kirov AS, Nehmeh SA, Erdi YE, Humm JL, Amols HI, et al. Validation of GATE Monte Carlo simulations of the GE Advance/Discovery LS PET scanners. Med Phys 2006;33 (1):198–208, Jan.
Bettinardi V, Danna M, Savi A, Lecchi M, Castiglioni I, Gilardi MC, et al. Performance evaluation of the new whole-body PET/CT scanner: discovery ST. Eur J Nucl Med Mol Imaging 2004;31:867–81.
Beyer T, Antoch G, Muller S, Egelhof T, Freudenberg LS, Debatin J, et al. Acquisition protocol considerations for combined PET/CT imaging. J Nucl Med 2004;45:25S–35S.
Townsend DW, Carney JPJ, Yap JT, Hall NC. PET/CT today and tomorrow. J Nucl Med 2004;45:4S–14S.
Carney JP, Townsend DW, Rappoport V, Bendriem B. Method for transforming CT images for attenuation correction in PET/CT imaging. Med Phys 2006;33 4:976–83, Apr.
Stabin M, Siegel J, Hunt J, Sparks R, Lipsztein J, Eckerman K. RADAR: the radiation dose assessment resource—an online source of dose information for nuclear medicine and occupational radiation safety [abstract]. J Nucl Med 2002;42 suppl:243P.
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.
Cristy M, Eckerman K. Specific absorbed fractions of energy at various ages from internal photons sources. Oak Ridge, TN: Oak Ridge National Laboratory; 1987:V1-V7. ORNL/TM-8381.
Stabin M, Watson E, Cristy M, Ryman J, Eckerman K, Davis J, et al. Mathematical models and specific absorbed fractions of photon energy in the nonpregnant adult female and at the end of each trimester of pregnancy. Oak Ridge, TN: Oak Ridge National Laboratory; 1995. ORNL report ORNL/TM-12907.
Sgouros G. Bone marrow dosimetry for radioimmunotherapy: theoretical considerations. J Nucl Med 1993;34:689–94.
Stabin MG, Siegel JA, Sparks RB, Eckerman KF, Breitz HB. Contribution to red marrow absorbed dose from total body activity: a correction to the MIRD Method. J Nucl Med 2001;42:492–8.
Antunes P, Ginj M, Zhang H, Waser B, Baum RP, Reubi JC, et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging 2007;34:982–93.
Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumors: molecular basis for in vivo multireceptor tumor targeting. Eur J Nucl Med Mol Imaging 2003;30:781–93.
Kwekkeboom DJ, Kooij PP, Bakker WH, Macke HR, Krenning EP. Comparison of 111In-DOTA-Tyr3-octreotide and 111In-DTPA-octreotide in the same patients: biodistribution, kinetics, organ and tumor uptake. J Nucl Med 1999;40:762–7.
Koukouraki S, Strauss LG, Georgoulias V, Schuhmacher J, Haberkorn U, Karkavitsas N, et al. Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumors scheduled for 90Y-DOTATOC therapy. Eur J Nucl Med Mol Imaging 2006;33 4:460–6, Apr.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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 35, 72–79 (2008). https://doi.org/10.1007/s00259-007-0587-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-007-0587-y