Pharmacokinetics and imaging properties in patients of 99mTc-N4-octreotate, a promising new radiopharmaceutical to image somatostatin receptor positive tumours

Full text: Technetium-99m labeled somatostatin (SST) analogues have a great potential in oncological nuclear medicine. The tetramine (N4)-derivatized octreotate (Demotate 1) can be labeled with 99mTc at high specific activities. This tracer shows a high affinity to SST receptors, high tumor uptake in an animal tumor model and high stability in vivo. The aim of this study was to evaluate the imaging properties and the pharmacokinetics of this promising new radiopharmaceutical in a small series of tumor patients. The study was approved by the local ethical committee. 99m Tc-labeling of Demotate 1 was performed under alkaline conditions at room temperature using 15 μg of peptide and 1,1-1,8 GBq 99mTc. After neutralization and sterile filtration the preparation was used without further purification. Radiochemical purity was determined by RP-gradient HPLC and TLC. Sterility of each preparation was checked. So far three patients have been included in the study. The diagnoses were: carcinoid tumor n=1 and endocrine pancreatic tumors n=2. All of them with a previously positive somatostatin receptor scintigraphy and tumor positive CT and/or ultrasound. Patients were injected with 500-550 MBq 99mTc-Demotate 1. Blood samples were taken at various time points up to 24 h p.i., urine was collected up to 6 h p.i. Planar images were acquired at 15-30 min, 1-2 h, 4 h and 24 h p.i. with additional SPECT imaging at 4 h. Radiochemical purity always exceeded 95 % up to 4 h p.i. Blood excretion was very rapid with <2 % ID in plasma after 1 h. Urinary excretion was rather low with <20 % ID alter 6 h and only intact peptide could be found in urine. Patients showed no sclinical signs of side effects due to the injected peptide. Somatostatin receptor positive tumors were rapidly visualized as early as 15 min p.i.. Organs of predominat normal uptake were the spleen and the kidneys. In contrast to other radiolabeled octreotide derivatives maximum tumor/organ ratios were already observed 1-2 h p.i. with tumor uptake also reaching a maximum (up to 19 % ID) at 1-2 h p.i.. All somatostatin receptor positive lesions visualized with 99mTc-Demotate were true positive in comparison to previous scintigraphies. 99mTc-N4 derivatized peptides for labeling with 99mTc show promising properties for receptor imaging in vivo. 99mTc-N4-Octreotate (Demotate 1) is suitable to image SST-receptor positive lesions in patients, shows rapid pharmacokinetics with some differences compared to 111In-DTPA-Octreotide. Further patient studies are currently performed. (author)