Page 114 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Chapter 5
intact in the blood, respectively (Fig. 4 C+D), indicating a clear increase of stability even with 2000 pmol peptide.
Biodistribution studies
The results of the biodistribution studies are displayed in Fig. 5. A maximum tumor uptake of 10.2±1.5 %ID/g tissue was reached using 2.5 MBq/200 pmol [111In]SB3 1 h p.i. in contrast to 19.7±3.5 % ID/g tissue after injection of [111In] SB3 + PA. At all studied time points, there was significantly higher (P<0.0001) tumor uptake when PA was co-administered with [111In]SB3. Next to tumor uptake, high radiotracer uptake was also observed in the GRPR-expressing pancreas and in the kidneys, the latter as a result of renal excretion and partial reabsorption of the radiopeptide. The increased in vivo stability of [111In]SB3 + PA also resulted in an increase in pancreatic uptake (4.1±2.3 vs 10.1±4.3 %ID/g tissue 1 h p.i. -/+ PA, respectively), while renal uptake remained similar (3.9±1.4 vs 4.5±1.4 %ID/g tissue 1 h p.i. -/+ PA, respectively). At 4 h and 24 h p.i. the same pattern was observed. A similar tumor to pancreas radioactivity ratio was found for [111In]SB3 +/- PA (3.4±2.5 vs 2.2±0.8, 1 h p.i. -/+ PA, respectively). The tumor to kidney ratio was more favorable however when the radiotracer was combined with PA (2.8±1.0 vs 4.8±2.2, 1 h p.i. -/+ PA respectively). Also, radiotracer uptake in the pancreas and the tumor was receptor-specific as can be concluded from the significantly decreased (P≤0.001) uptake when an excess of unlabeled SB3 was co-administered.
SPECT/MRI
In line with the biodistribution studies, SPECT/MR imaging performed 1 h, 4 h and 24 h p.i. of 25 MBq/200 pmol [111In]SB3 +/- PA resulted in clearly improved tumor visualization when the radiotracer was combined with PA, at all imaging time points (Fig. 6 A). ROI analysis showed an increase of 70% in signal intensity (1424 vs 2434 kBq/mL) 1 h p.i. of [111In]SB3 only and [111In]SB3 + PA, respectively. Intensity curves and the biodistribution time activity curves were normalized to 100% at 1 h for the + PA group. The normalized curves obtained from SPECT/MR images and biodistribution studies showed a well-comparable pattern for the tumor radioactivity (Fig. 6 B).
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