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Published in: European Journal of Nuclear Medicine and Molecular Imaging 4/2006

01-04-2006 | Original article

Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy

Authors: Sophia Koukouraki, Ludwig G. Strauss, Vassilios Georgoulias, Jochen Schuhmacher, Uwe Haberkorn, Nikolaos Karkavitsas, Antonia Dimitrakopoulou-Strauss

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 4/2006

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Abstract

Purpose

The purpose of the study was to evaluate the pharmacokinetics of 68Ga-DOTATOC in order to ascertain which parameters have the greatest impact on the global DOTATOC standardised uptake value (SUV), defined as the mean SUV of the last frame of the dynamic study 55–60 min p.i.

Methods

Twenty-two patients with 74 metastatic lesions were examined with dynamic 68Ga-DOTATOC PET studies. Standardised uptake values (SUVs) were calculated for all frames following the injection of the tracer. We defined global SUV as the mean SUV of the last frame (frame duration 5 min) of the dynamic study 55–60 min p.i. A two-tissue compartment model with a blood compartment was used for the evaluation of the rate constants k 1 (receptor binding), k 2 (displacement from the receptor), k 3 (cellular internalisation), k 4 (cellular externalisation) and fractional blood volume (Vb). Furthermore, a non-compartmental model was applied for calculation of the fractal dimension (FD) of the time-activity curves based on the box counting procedure.

Results

Qualitative analysis revealed increased uptake of 68Ga-DOTATOC in 21/22 patients and in 72/74 lesions. The SUV for 68Ga-DOTATOC was highly variable, with a range from 0.877 to 28.07 (mean 8.73). The highest uptake was measured in a patient with a NET of the pancreas and the lowest in a patient with a medullary thyroid carcinoma (MEN II). The quantitative evaluation based on the compartmental analysis revealed high receptor binding (k 1) and internalisation (k 3) for 68Ga-DOTATOC, and low cellular externalisation (k 4) as well as a relatively low fractional blood volume (Vb). The FD values varied from 1.10 to 1.45, with a mean of 1.33. No significant linear correlation was found for k 1 and k 3. A low, linear correlation was noted for k 1 and Vb (r=0.25,p=0.03), and there was a significant non-linear correlation between SUV and FD (r=0.74, p<0.001). Best subset analysis demonstrated that k 1 had the greatest impact on the global SUV, followed by Vb and k 3.

Conclusion

DOTATOC uptake in NETs is mainly dependent on k 1 (receptor binding) and Vb (fractional blood volume). Pharmacokinetic data analysis can help to separate blood background activity (Vb) from the receptor binding (k 1), which may help to optimise planning of 90Y-DOTATOC therapy.
Literature
1.
go back to reference Kaltsas G, Besser M, Grossman A. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev 2004;25:458–511PubMedCrossRef Kaltsas G, Besser M, Grossman A. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev 2004;25:458–511PubMedCrossRef
2.
go back to reference Reubi JC, Laissue J, Waser B, Horisberger U, Schaer JC. Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann N Y Acad Sci 1994;733:122–37PubMedCrossRef Reubi JC, Laissue J, Waser B, Horisberger U, Schaer JC. Expression of somatostatin receptors in normal, inflamed, and neoplastic human gastrointestinal tissues. Ann N Y Acad Sci 1994;733:122–37PubMedCrossRef
3.
go back to reference Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med 1991;32:623–48PubMed Strauss LG, Conti PS. The applications of PET in clinical oncology. J Nucl Med 1991;32:623–48PubMed
4.
go back to reference Dimitrakopoulou-Strauss A, Strauss LG, Schwarzbach M, Burger C, Heichel T, Willeke F, et al. Dynamic PET18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading. J Nucl Med 2001;42:713–20PubMed Dimitrakopoulou-Strauss A, Strauss LG, Schwarzbach M, Burger C, Heichel T, Willeke F, et al. Dynamic PET18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading. J Nucl Med 2001;42:713–20PubMed
5.
go back to reference Adams S, Baum R, Rink T, Schumm-Dräger PM, Usadel KH, Hör G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 1998;25:79–83PubMedCrossRef Adams S, Baum R, Rink T, Schumm-Dräger PM, Usadel KH, Hör G. Limited value of fluorine-18 fluorodeoxyglucose positron emission tomography for the imaging of neuroendocrine tumours. Eur J Nucl Med 1998;25:79–83PubMedCrossRef
6.
go back to reference Pacak K, Eisenhofer G, Goldstein DS. Functional imaging of endocrine tumors: role of positron emission tomography. Endocr Rev 2004;25:568–80PubMedCrossRef Pacak K, Eisenhofer G, Goldstein DS. Functional imaging of endocrine tumors: role of positron emission tomography. Endocr Rev 2004;25:568–80PubMedCrossRef
7.
go back to reference De Jong M, Breeman WA, Bernard BF, van Gameren A, de Bruin E, Bakker WH, et al. [DOTA0,TYR3] octreotide is dependent on the peptide amount. Eur J Nucl Med 1999;26:693–8PubMedCrossRef De Jong M, Breeman WA, Bernard BF, van Gameren A, de Bruin E, Bakker WH, et al. [DOTA0,TYR3] octreotide is dependent on the peptide amount. Eur J Nucl Med 1999;26:693–8PubMedCrossRef
8.
go back to reference De Jong M, Bakker WH, Krenning EP, Breeman WA, van der Pluijm ME, Bernard BF, et al. Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1, Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy. Eur J Nucl Med 1997;24:368–71PubMedCrossRef De Jong M, Bakker WH, Krenning EP, Breeman WA, van der Pluijm ME, Bernard BF, et al. Yttrium-90 and indium-111 labelling, receptor binding and biodistribution of [DOTA0,d-Phe1, Tyr3]octreotide, a promising somatostatin analogue for radionuclide therapy. Eur J Nucl Med 1997;24:368–71PubMedCrossRef
9.
go back to reference Bohuslavizki KH, Brenner W, Braunsdorf WE, Behnke A, Tinnemeyer S, Hugo HH, et al. Somatostatin receptor scintigraphy in the differential diagnosis of meningioma. Nucl Med Commun 1996;17:302–10PubMedCrossRef Bohuslavizki KH, Brenner W, Braunsdorf WE, Behnke A, Tinnemeyer S, Hugo HH, et al. Somatostatin receptor scintigraphy in the differential diagnosis of meningioma. Nucl Med Commun 1996;17:302–10PubMedCrossRef
10.
go back to reference Maecke H, Hofmann M, Haberkorn U. 68-Ga-labeled peptides in tumor imaging. J Nucl Med 2005;46:172S–8SPubMed Maecke H, Hofmann M, Haberkorn U. 68-Ga-labeled peptides in tumor imaging. J Nucl Med 2005;46:172S–8SPubMed
11.
go back to reference Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem 2000;7:971–94PubMed Heppeler A, Froidevaux S, Eberle AN, Maecke HR. Receptor targeting for tumor localisation and therapy with radiopeptides. Curr Med Chem 2000;7:971–94PubMed
12.
go back to reference Kontaxakis G, Strauss LG, Thireou T, Ledesma-Carbayo MJ, Santos A, Pavlopoulos SA et al. Iterative image reconstruction for clinical PET using ordered subsets, median root prior, and a web-based interface. Mol Imaging Biol 2002;4:219–31PubMedCrossRef Kontaxakis G, Strauss LG, Thireou T, Ledesma-Carbayo MJ, Santos A, Pavlopoulos SA et al. Iterative image reconstruction for clinical PET using ordered subsets, median root prior, and a web-based interface. Mol Imaging Biol 2002;4:219–31PubMedCrossRef
13.
go back to reference Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, et al. Characterization of (68Ga)-DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) kinetics in patients with meningiomas J Nucl Med 2005;46:763–9PubMed Henze M, Dimitrakopoulou-Strauss A, Milker-Zabel S, Schuhmacher J, Strauss LG, Doll J, et al. Characterization of (68Ga)-DOTA-D-Phe1-Tyr3-octreotide (DOTATOC) kinetics in patients with meningiomas J Nucl Med 2005;46:763–9PubMed
14.
go back to reference Burger C, Buck A. Requirements and implementations of a flexible kinetic modeling tool. J Nucl Med 1997;38:1818–23PubMed Burger C, Buck A. Requirements and implementations of a flexible kinetic modeling tool. J Nucl Med 1997;38:1818–23PubMed
15.
go back to reference Ohtake T, Kosaka N, Watanabe T, Yokoyama I, Moritan T, Masuo M,, et al. Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. J Nucl Med 1991;32:1432–8PubMed Ohtake T, Kosaka N, Watanabe T, Yokoyama I, Moritan T, Masuo M,, et al. Noninvasive method to obtain input function for measuring tissue glucose utilization of thoracic and abdominal organs. J Nucl Med 1991;32:1432–8PubMed
16.
go back to reference Dimitrakopoulou–Strauss A, Strauss LG, Mikolajczyk K, Burger C, Lehnert T, Bernd L, et al. On the fractal nature of dynamic positron emission tomography (PET) studies. World J Nucl Med 2003;2:306–13 Dimitrakopoulou–Strauss A, Strauss LG, Mikolajczyk K, Burger C, Lehnert T, Bernd L, et al. On the fractal nature of dynamic positron emission tomography (PET) studies. World J Nucl Med 2003;2:306–13
17.
go back to reference Hofmann M, Maecke H, Börner R, Weckesser E, Schoffski P, Oei L, et al. Biokinetics and imaging with the somatostatin receptor PET radioligand68Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001;28:1751–7PubMedCrossRef Hofmann M, Maecke H, Börner R, Weckesser E, Schoffski P, Oei L, et al. Biokinetics and imaging with the somatostatin receptor PET radioligand68Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001;28:1751–7PubMedCrossRef
18.
go back to reference Baish JW, Jain RK. Fractals and cancer. Cancer Res 2001;61:8347–50 Baish JW, Jain RK. Fractals and cancer. Cancer Res 2001;61:8347–50
19.
go back to reference Majumdar S, Link TM, Millard J, Lin JC, Augat P, Newitt D, et al. In vivo assessment of trabecular bone structure using fractal analysis. Med Phys 2000;27:2594–9PubMedCrossRef Majumdar S, Link TM, Millard J, Lin JC, Augat P, Newitt D, et al. In vivo assessment of trabecular bone structure using fractal analysis. Med Phys 2000;27:2594–9PubMedCrossRef
20.
go back to reference Kuikka JT, Hartikainen P. Heterogeneity of cerebral blood flow: a fractal approach. Nuklearmedizin 2000;39:37–42PubMed Kuikka JT, Hartikainen P. Heterogeneity of cerebral blood flow: a fractal approach. Nuklearmedizin 2000;39:37–42PubMed
Metadata
Title
Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy
Authors
Sophia Koukouraki
Ludwig G. Strauss
Vassilios Georgoulias
Jochen Schuhmacher
Uwe Haberkorn
Nikolaos Karkavitsas
Antonia Dimitrakopoulou-Strauss
Publication date
01-04-2006
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 4/2006
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-005-0006-1

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