New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy.
QUARTERLY JOURNAL OF NUCLEAR MEDICINE(2000)
Abstract
In vitro data have demonstrated a high amount of receptors for various hormones and peptides on malignant cells of neuroendocrine origin. Among these, binding sites for members of the SST-family (hSSTR1-5) are frequently found, and their expression has led to therapeutic and diagnostic attempts to specifically target these receptors. Receptor scintigraphy using radiolabeled peptide ligands has proven its effectiveness in clinical practice. In addition, initial results have indicated a clinical potential for receptor-targeted radiotherapy. Based on somatostatin (SST) receptor (R) recognition, the novel radiopharmaceuticals In-111/Y-90-DOTA-lanreotide developed at the University of Vienna as well as In-111/Y-90-DOTA-DPhe(1)-Tyr(3)-octreotide (NOVARTIS) both have provided promising data for diagnosis and treatment of hSSTR-positive tumors. SSTR scintigraphy using In-111-DTPA-DPhe(1)-octreotide has a high positive predictive value for the vast majority of neuroendocrine tumors and has gained its place in the diagnostic work-up as well as follow-up of patients. We have used In-111-DOTA-lanreotide scintigraphy in 166 patients since 1997 and have seen positive results in 93% of patients. In 42 patients with neuroendocrine tumors comparative data were obtained. As opposed to In-111-DTPA-DPhe(1)-octreotide and In-111-DOTA-DPhe(1)-'Tyr(3)-octreotide, discrepancies in the scintigraphic results were seen in about one third of patients concerning both the tumor uptake as well as tumor lesion detection. Initial results both with Y-90-DOTA-lanreotide as well as Y-90-DOTA-DPhe(1)-Try(3)-octreotide has pointed out the clinical potential of radionuclide receptor-targeted radiotherapy. This new therapy could offer palliation and disease control at a reduced cost. The final peptide therapy strategy is most probably cheaper than conventional radiotherapies or prolonged chemotherapies. Overall, receptor-mediated radiotherapy with Y-90-DOTA-lanreotide/Y-90-DOTA-DPhe(1)-TYr(3)-octreotide might also be effective in patients refractory to conventional strategies.
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Key words
receptors, somatostatin,somatostatin analogs and derivatives,octreotide,neuroendocrine tumors, radiotherapy
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