Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy
- 527 Downloads
The purpose of this study was to evaluate and compare, by means of dynamic PET, the pharmacokinetics of 68Ga-DOTATOC, a tracer which reflects the expression of somatostatin receptors (SSTRs), and of [18F]FDG, a marker of tumour viability, in patients with metastatic neuroendocrine tumours (NETs) in whom 90Y-DOTATOC therapy was planned.
Materials and methods
Fifteen patients (63 lesions) with confirmed metastatic NETs were enrolled in this study. Dynamic [18F]FDG and 68Ga-DOTATOC PET scans were performed on two different days in the same week. The data analysis was based on qualitative and quantitative analysis using a two-tissue compartment model with a blood compartment and a non-compartment model based on the fractal dimension (FD). Multivariate analysis was used for evaluation of the kinetic data.
Enhanced [18F]FDG uptake was observed in 43/63 lesions. 68Ga-DOTATOC showed pathologically enhanced uptake in all evaluated patients and in 57/63 lesions. Discordant scintigraphic results for [18F]FDG and 68Ga-DOTATOC were observed in 6/15 patients. Global SUV was defined as the SUV measured in the last frame (55–60 min p.i.) of the dynamic series, for each tracer. The median global SUV uptake was 7.9 for 68Ga-DOTATOC and 4.6 for [18F]FDG. The selection of patients for 90Y-DOTATOC therapy was based on the uptake of 68Ga-DOTATOC. Multiple linear regression analysis was applied to determine the effect of each kinetic parameter (K 1–k 4, V B) on the global SUV of both tracers. The highest positive t-ratio was found for K 1 (receptor binding), followed by k 3 (cellular internalisation) and V B (fractional blood volume), when using the global 68Ga-DOTATOC uptake (SUV) as a target variable. Analysis of the [18F]FDG data revealed the highest positive t-ratio for V B, followed by k 3 (phosphorylation) and K 1 (influx). The comparison of global SUV, K 1–k 4 and the FD for [18F]FDG and 68Ga-DOTATOC did not show any statistically significant correlation. The only parameter that demonstrated a significant linear correlation between the tracers was V B.
68Ga-DOTATOC is a promising tool for evaluation of the expression of SSTR2 in NETs. The combination of [18F]FDG and 68Ga-DOTATOC dynamic PET studies provides different information regarding the biological properties of lesions in patients with metastatic NETs in whom 90Y-DOTATOC therapy is planned. While the global 68Ga-DOTATOC uptake is influenced mostly by K 1, the global [18F]FDG uptake is mostly influenced by V B. Only patients with enhanced 68Ga-DOTATOC uptake (SUV >5.0) were referred to 90Y-DOTATOC therapy.
Keywords[18F]FDG 68Ga-DOTATOC Neuroendocrine tumours Kinetic analysis
We thank Prof. Dr. Helmut R. Mäcke (University Hospital Basel, Switzerland) for providing sample material of DOTATOC.
- 6.Eisenwiener KP, Prata MI, Buschmann I, Zhang HW, Santos AC, Wenger S, et al. NODAGATOC, a new chelator-coupled somatostatin analogue labelled with [67/68Ga] and [111In] for SPECT, PET, and targeted therapeutic applications of somatostatin receptor (hsst2) expressing tumors. Bioconjugate Chem 2002;13:530–541CrossRefGoogle Scholar
- 8.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;2:306–313Google Scholar
- 9.Toorongian SA, Mulholland GK, Jewett DM, Bachelor MA, Kilbourn MR. Routine production of 2-deoxy-2 (18F)fluoro-D-glucose by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin. Nucl Med Biol 1990;3:273–279Google Scholar
- 16.Foley AL, Lyles RH, Sprouse JT, Conrad EU 3rd, Eary JF. (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. Clin Cancer Res 2000;6:1279–1287Google Scholar
- 18.Belhocine T, Foidart J, Rigo P, Najjar F, Thiry A, Quatresooz P, et al. Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. Nucl Med Commun 2002;23:727–734PubMedCrossRefGoogle Scholar
- 19.Leboulleux S, Dromain C, Bonniaud G, Auperin A, Caillou B, Lumbroso J, et al. Diagnostic and prognostic value of 18-fluorodeoxyglucose positron emission tomography in adrenocortical carcinoma: a prospective comparison with computed tomography. J Clin Endocrin Metab 2006;91:920–925CrossRefGoogle Scholar
- 25.Dimitrakopoulou-Strauss A, Georgoulias V, Schuhmacher J, Herth F, Koukouraki S, Maecke HR, et al. Quantitative assessment of SSTR2 expression in patients with non-small cell lung cancer using 68Ga-DOTATOC PET and comparison to F-18-FDG. Eur J Nucl Med Mol Imaging 2006; in press. DOI10.1007/s00259-005-0063-5Google Scholar