One of the goals of this proposed research is to increase the number of radioligands available for the labeling with the positron emitting isotope Ga-68 and the readily available gamma-emmiter in-111. Specifically, efforts will focus on the synthesis of a new diaminoethane dithiol bifunctional chelate that has been found to have the highest stability for Ga(III) and in(III). This chelate be conjugated to a somatostatin analogue, octreotide. Certain cancerous tumors contain a large number of somatostatin receptors, therefore octreotide-radiometal conjugates can be used to diagnose and treat certain cancers by binding to somatostatin receptor and including a growth inhibitory effect in these tissues. The ability of this diaminoethane dithiol-octreotide- radiometal conjugate to bind somatostatin receptors will be determined using AtT-20 mouse pituitary carcinoma cells. The biodistribution and metabolism the conjugate will be determined using normal Sprague-Dawley rate. Biodistribution studies will be accomplished by extracting the activity from the various organs and counting each sample using a gamma- counter. The metabolism of the complex will be analyzed using HPLC and radio-TLC. The second goal of this proposal is to evaluate radiolabeled octreotide as a radiotherapeutic agent using tumor-bearing rats. This will involve new production techniques for 64Cu at Washington University, the preparation of 64Cu-chelate-octreotide and the manipulation of a tumor-bearing rat model for evaluation of therapeutic efficacy of 64Cu. Tumor growth inhibition will be evaluated by determining the % survival of animals per week post-treatment. At the time of their death the rats will be dissected and the tumors weighed.
| Bass, L A; Lanahan, M V; Duncan, J R et al. (1998) Identification of the soluble in vivo metabolites of indium-111-diethylenetriaminepentaacetic acid-D-Phe1-octreotide. Bioconjug Chem 9:192-200 |
| Anderson, C J; Jones, L A; Bass, L A et al. (1998) Radiotherapy, toxicity and dosimetry of copper-64-TETA-octreotide in tumor-bearing rats. J Nucl Med 39:1944-51 |
