Biological Characterisation of [⁶⁷Ga] or [⁶⁸Ga] Labelled DFO-Octreotide (SDZ 216-927) for PET Studies of Somatostatin Receptor Positive Tumors

Summary

Radiolabelled analogues of Somatostatin (SRIF) were demonstrated to be useful for conventional gamma-camera imaging of SRIF receptor-positive tumors and their metastases. To evaluate the feasibility of positron emission tomography (PET) or SRIF receptor-positive tumors deferoxamine (DFO) was conjugated to octreotide via a succinyl linker to form a stable conjugate with the gallium isotopes ⁶⁷Ga and ⁶⁸Ga. This new octreotide analog, SDZ 216-927, binds specifically and with high affinity to SRIF receptors in vitro (pK_i = 8.94±0.06) and exhibits SRIF like biological properties as demonstrated by the inhibition of growth hormone (GH) release from cultured pituitary cells. SDZ 216-927 was efficiently labelled with ⁶⁷Ga without affecting high affinity binding to SRIF receptors. Biodistribution studies revealed that [⁶⁷Ga]SDZ 216-927 was stable in vivo and rapidly cleared from the circulation, as indicated by the low amount of ⁶⁷Ga detected in the blood four hours post injection (p.i.). SRIF receptor-positive tumors were clearly visualized 10 minutes p.i. in tumor bearing rats. The specificity of ligand binding in vivo was demonstrated i) by the high tumor/non-tumor ratio 4 hours p.i. (tumor/blood 22.3:1, tumor/muscle 64.5:1, tumor/liver 4.0:1, tumor/spleen 16.8:1) and ii) by a significantly lower uptake of radioactivity in the tumor after pretreatment of tumor bearing animals with an excess of unlabelled SDZ 216-927. SDZ 216-927, when labelled with the positron emitting isotope ⁶⁸Ga, clearly imaged SRIF receptor-positive tumors using positron emission tomography (PET). Therefore quantitative SRIF receptor imaging with PET seems to be possible using this new radiopharmaceutical.

Key words

Somatostatin Receptor - Radiodiagnosis - Positron Emission Tomography - Gallium-67 - Gallium-68 - Exocrine Pancreatic Tumor - Rat