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

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Abstract
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. 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. 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, pk 1 had the greatest impact on the global SUV, followed by Vb and k 3. 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.