Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors Journal Article
| Authors: | Ugur, O.; Kothari, P. J.; Finn, R. D.; Zanzonico, P.; Ruan, S.; Guenther, I.; Maecke, H. R.; Larson, S. M. |
| Article Title: | Ga-66 labeled somatostatin analogue DOTA-DPhe1-Tyr3-octreotide as a potential agent for positron emission tomography imaging and receptor mediated internal radiotherapy of somatostatin receptor positive tumors |
| Abstract: | Radionuclide labeled somatostatin analogues selectively target somatostatin receptor (SSTR)-expressing tumors as a basis for diagnosis and treatment of these tumors. Recently, a DOTA-functionalized somatostatin analogue, DOTATOC (DOTA-DPhe1-Tyr3-octreotide) has been developed. This compound has been shown to be superior to the other somatostatin analogues as indicated by its uniquely high tumor-to-non-target tissue ratio. DOTATOC can be labeled with a variety of radiometals including gallium radioisotopes. Gallium-66 is a positron emitting radionuclide (T1/2 =9.5 hr; β+=56%), that can be produced in carrier free form by a low-beam energy cyclotron. In this study we investigated SSTR targeting characteristics of 66Ga-DOTATOC in AR42J rat pancreas tumor implanted nude mice as a potential agent for diagnosis and receptor-mediated internal radiotherapy of SSTR-expressing tumors. We compared our results with 67Ga- and 68Ga- labeled DOTATOC. The radiolabeling procedure gave labeling yield ranged from 85-95% and radiochemical and chemical purity was > 95%. In-vitro competitive binding curves and in-vivo competitive displacement studies with an excess of unlabeled peptide indicates that there is specific binding of the radioligand to SSTR. Animal biodistribution data and serial microPET™ images demonstrated rapid tumor uptake and rapid clearance from the blood and all tissues except kidney. Maximum % ID/g values for tumor were 10.0 ± 0.7, 13.2 ± 2.1 and 9.8 ± 1.5 for 66Ga-, 67Ga-, and 68Ga-DOTATOC, respectively. Calculated tumor, kidney and bone marrow doses for 66Ga-DOTATOC based on biodistribution data were 178, 109 and 1.2 cGy/MBq, respectively. We conclude that 66Ga labeled DOTATOC can be used for PET diagnosis and quantitative imaging-based dosimetry of SSTR positive tumors. 66Ga-DOTATOC may also be used in higher doses for ablation of these tumors. However, kidney is the critical organ for toxicity (tumor/kidney ratio = 1.64), and high kidney uptake must be eliminated before devising a therapy protocol. © 2002 Elsevier Science Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; nonhuman; drug targeting; pancreatic neoplasms; positron emission tomography; radiopharmaceuticals; animals; mice; bone marrow; tumor cells, cultured; kidney; drug distribution; drug uptake; isotope labeling; dosimetry; pancreas tumor; rat; positron-emission tomography; drug clearance; rats; octreotide; chromatography, high pressure liquid; radioisotope; ligand binding; 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid; somatostatin derivative; radiochemistry; gallium; radioassay; gallium radioisotopes; article; octreotide[1 dextro phenylalanine 3 tyrosine 1,4,7,10 tetraazacyclododecane 1,4,7,10 tetraacetic acid] ga 66; receptors, somatostatin |
| Journal Title: | Nuclear Medicine and Biology |
| Volume: | 29 |
| Issue: | 2 |
| ISSN: | 0969-8051 |
| Publisher: | Elsevier Science Inc. |
| Date Published: | 2002-02-01 |
| Start Page: | 147 |
| End Page: | 157 |
| Language: | English |
| DOI: | 10.1016/s0969-8051(01)00290-6 |
| PUBMED: | 11823119 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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