Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.
OBJECTIVE
The purpose of the study was to evaluate the pharmacokinetics of (68)Ga-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 (68)Ga-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 (V(b)). 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 (68)Ga-DOTATOC in 21/22 patients and in 72/74 lesions. The SUV for (68)Ga-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 (68)Ga-DOTATOC, and low cellular externalisation (k (4)) as well as a relatively low fractional blood volume (V(b)). 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 V(b) (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 V(b) and k (3).


CONCLUSIONS
DOTATOC uptake in NETs is mainly dependent on k (1) (receptor binding) and V(b) (fractional blood volume). Pharmacokinetic data analysis can help to separate blood background activity (V(b)) from the receptor binding (k (1)), which may help to optimise planning of (90)Y-DOTATOC therapy.
Koukouraki
Sophia
S
Medical PET Group, Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Strauss
Ludwig G
LG
Georgoulias
Vassilios
V
Schuhmacher
Jochen
J
Haberkorn
Uwe
U
Karkavitsas
Nikolaos
N
Dimitrakopoulou-Strauss
Antonia
A
D000368:Aged; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy / Q000556:secondary*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D014018:Tissue Distribution
C499142:Ga(III)-DOTATOC; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C496730:90Y-octreotide, DOTA-Tyr(3)-; D015282:Octreotide