First clinical evaluation of somatostatin receptor antagonist imaging

Objectives For several years somatostatin receptor antagonists have not been considered for tumor targeting because they do not internalize into tumor cells. Ginj et al. have demonstrated that somatostatin receptor 2 (sst2) expressing cells provide significantly more binding sites for receptor antagonists than for receptor agonists (Ginj et al. PNAS 2006). Our goal was to prospectively compare sst2 antagonist (111In-DOTABASS) vs. agonist (111In-OctreoScan) imaging in patients with neuroendocrine tumors (NETs).

Methods Five patients with metastatic NETs (5 male, age 63 ± 7,1 years, 1 thyroid cancer, 4 midgut NETs) were examined with ~190 MBq 111In-OctreoScan and ~160 MBq 111In-DOTABASS 11 - 13 days apart. Whole-body planar images were obtained at 0.5, 1, 4, 24, 48 and 72h after injection of 111In-DOTABASS (111In-OctreoScan: 4 and 24h p.i.). SPECT images of the abdomen and thorax were performed at 5h p.i. For estimating the radiation dose, it was assumed that 111In-DOTABASS shows an identical biodistribution as 90Y-DOTABASS.

Results No adverse-effects of ~20 μg 111In-DOTABASS were observed. In a lesion based analysis 111In-DOTABASS detected 42 lesions whereas 111In-OctreoScan detected only 24 lesions. 111In-DOTABASS showed an approximately three times higher tumor-to-kidney uptake ratio than 111In-OctreoScan. The estimated kidney (1.92 mGy/MBq), liver (0.26 mGy/MBq) and spleen (1.01 mGy/MBq) doses for 90Y-DOTABASS are less as previously reported for 90Y-DOTATOC (Forrer et al. EJNMMI 2004).

Conclusions Imaging of neuroendocrine tumors with sst2 antagonists is feasible in patients. As suggested by preclinical studies, 111In-DOTABASS provided a better visualization of metastatic NETs than 111In-OctreoScan. It is likely that the antagonist approach will have significant impact on peptide receptor mediated imaging and treatment in patients