New octreotide derivatives for in vivo 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 67Ga and 68Ga (DFO-SMS, Fig. 1a) and 99mTc (PnAO-SMS, Fig. 1b) have been synthesized and evaluated in vitro and in vivo in tumor bearing rats. DFO-SMS can be labeled with 67Ga3+ and 68Ga3+ 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 [68Ga]-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 99mTc 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.