NEW OCTREOTIDE DERIVATIVES FOR INVIVO TARGETING OF SOMATOSTATIN RECEPTOR-POSITIVE TUMORS FOR SINGLE-PHOTON EMISSION COMPUTED-TOMOGRAPHY (SPECT) AND POSITRON EMISSION TOMOGRAPHY (PET)

Two new modifications of the somatostatin analog octreotide, designed to hold the gallium isotopes Ga-67 and Ga-68 (DFO-SMS, Fig. 1 a) and Tc-99m (PnAO-SMS, Fig. 1b) have been synthesized and evaluated in vitro and in vivo in tumor bearing rats. DFO-SMS can be labeled with Ga-67(3+) and Ga-68(3+) with high specific activity within less than 30 minutes in a ''cold kit'' type formulation. The labeled conjugate is stable under physiological conditions. Moreover the binding affinity to somatostatin receptors on rat brain cortex membranes was shown to be retained. In vivo fast tumor localization was demonstrated and the pharmacokinetics proved to be favourable as the main excretion route was via the kidneys. First PET studies with [Ga-68]-DFO-SMS showed a rapid accumulation in the tumor and a residence half-life at the tumor site of about 6 hours. PnAO-SMS can be labeled with Tc-99m with high radiochemical purity. In vivo the radiotracer accumulates well in the tumor but due to its high lipophilicity, its main excretion route is via the hepatobiliary system.