Comparative orbital scintigraphy with technetium-99m-P829, indium-111-DOTA-Lanreotide and DOTA-Tyr3-octreotide in Graves disease

Aim: Receptors (R) for somatostatin (SST) are expressed on various tumor cells as well as activated leukocytes and other lymphoproliferative and immune cells. Our previous data have shown that various SST analogs including 111In-OctreoScan, 111In-DOTA-Lanreotide (DLAN), 111In-DOTA-Tyr3-Octreotide (DTOCT) and 99mTc-P829 bind with high affinity onto many different types of tumor cells as well as to leukocytes via hSSTR target receptors. We have evaluated the orbital uptake of these tracers in patients with active and inactive thyroid-associated orbitopathy. Material and Methods: Clinical grade of the orbital disease was documented in all patients (n=90) by the NOSPECS classification, the clinical activity score (CAS) as well as the supra nasal index (SNI) measured by standardized echography. 99mTc-P829 scintigraphy (740 MBq) or scintigraphy with one of the 111In-labeled SST analogs (150 MBq) was performed in patients with thyroid-associated orbitopathy (duration of the disease: 1 - 360 months). In patients undergoing 99mTc-P829 scintigraphy, SPECT (360 deg.) and planar studies were completed within 3 h post injection, whereas most patients undergoing scintigraphy with 111In-labeled SST analogs also had a 24 h image acquisition. Orbital (O) regions of interest (ROIs) were opposed to temporo-parietal (TP) and occipital (OCC) ROIs and the O/TP and O/OCC ratios were calculated. Uptake ratios in Graves disease were compared to orbital data calculated from cancer patients without eye disease. Results: Compared to clinical data, a significant correlation was found only for CAS (p<0.01; r=0.74), whereas the NOSPECS classification as well as the SNI did not correlate with the uptake of either of the SST tracers. Overall, the image quality was found best for 99mTc-P829 images (three independent observers) despite of somewhat lower uptake both for O/TP as well as O/OCC uptake ratios. 111In-DLAN and 111In-DTOCT biokinetics were comparable in Graves disease patients showing a rapid blood clearance and visualization of the orbit within minutes of injection. In patients without active disease (O/(TP+OCC) / 2 ratio: 1.20 +/- 0.09) as well as in control patients (O / (TP+OCC) /2 ratio: 1.19 +/- 0.07) the orbit itself appeared as cold area. Visual orbital accumulation was found in all patients with active Graves ophthalmopathy (99mTc-P829 uptake: O / (TP+OCC)/2 ratio: 1.5 +/- 0.09; 111In-DLAN uptake: O / (TP+OCC)/2 ratio: 1.78 +/- 0.09, 111In-DTOCT ratio: 1.83 +/- 0.08 (p<0.01) in the control group. With all three tracers, patients with active eye disease showed an increased orbital uptake as compared to patients with inactive disease (p<0.01). Conclusion: 99mTc-P829, 111In-DLAN and 111In-DTOCT, all three yield high orbital binding for active orbitopathy associated with thyroid Graves disease. In-house availability of 99mTc-P829, cost-effectiveness, lower radiation dose, shorter acquisition protocol and better image quality favor SSTR scintigraphy with 99mTc-P829 over 111In-labeled compounds