Publications (2)12.67 Total impact
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Article: Radiotherapy and dosimetry of 64Cu-TETA-Tyr3-octreotate in a somatostatin receptor-positive, tumor-bearing rat model.
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ABSTRACT: 64Cu [T1/2 = 12.8 h; beta+ = 0.655 MeV (19%); beta- = 0.573 MeV (40%)] has shown promise as a radioisotope for targeted radiotherapy. It has been demonstrated previously that the somatostatin analogue 64Cu-TETA-octreotide (64Cu-TETA-OC, where TETA is 1,4,8,11-tetraazacyclotetradecane-N,N',N",N"'-tetraacetic acid) significantly inhibited the growth of somatostatin receptor-positive CA20948 rat pancreatic tumors in Lewis rats (C. J. Anderson et al., J. Nucl. Med., 39: 1944-1951, 1998). In this study, we evaluated the radiotherapeutic efficacy of a new 64Cu-labeled somatostatin analogue, 64Cu-TETA-Tyr3-octreotate (64Cu-TETA-Y3-TATE), in CA20948 tumor-bearing rats. A single dose of 15 mCi (555 MBq) of 64Cu-TETA-Y3-TATE was shown to be more effective in reducing tumor burden than the same dose of 64Cu-TETA-OC. In multiple dose experiments, tumor-bearing rats were administered three doses of either 10 or 20 mCi (370 or 740 MBq) of 64Cu-TETA-Y3-TATE at 48-h intervals. Rats given 3x10 mCi (3x370 MBq) showed extended mean survival times compared with rats given a single dose; however, no complete regressions occurred. Complete regression of tumors was observed for all rats treated with 3x20 mCi (3x740 MBq), with no palpable tumors for approximately 10 days; moreover, the mean survival time of these rats was nearly twice that of controls. Toxicity was determined by physical appearance and hematological and enzyme analysis, which revealed no overt toxicity and only transient changes in blood and liver chemistry. Absorbed dose estimates showed the dose-limiting organ to be the kidneys. The radiotherapy results, along with absorbed dose estimates to target and clearance organs, confirm that 64Cu-labeled somatostatin analogues warrant continued consideration as agents for targeted radiotherapy.Clinical Cancer Research 12/1999; 5(11):3608-16. · 7.74 Impact Factor -
Article: Identification of the soluble in vivo metabolites of indium-111-diethylenetriaminepentaacetic acid-D-Phe1-octreotide.
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ABSTRACT: Indium-111-diethylenetriaminepentaacetic Acid-D-phenylalanine-octreotide ([111]In-DTPA-octreotide) is a cyclic eight amino acid somatostatin analogue which is approved for gamma scintigraphy of neuroendocrine tumors. To address the factors that contribute to liver and kidney retention of this radiopharmaceutical, its metabolism was evaluated in normal and tumor-bearing rats. The soluble fractions from nontarget (liver and kidney) and target (tumor, pancreas, adrenals) organ homogenates were analyzed out to 21 h postinjection, and urine was analyzed out to 12 h postinjection. The blood was analyzed at shorter time intervals due to the rapid clearance of (111)In-DTPA-octreotide. Radio-TLC and HPLC were used to analyze organ homogenates, blood, and urine. By TLC, intact (111)In-DTPA-octreotide was resolved from the soluble metabolites, and a similar apparent rate of metabolism was observed in the liver, kidney, tumor, and pancreas with approximately 30% intact (111)In-DTPA-octreotide at 4 h postinjection. In the adrenals, metabolism occurred more slowly with approximately 60% intact (111)In-DTPAoctreotide at 4 h postinjection. At 4 h postinjection, the activity excreted in the urine consisted of 85% intact (111)In-DTPA-octreotide. HPLC provided resolution of the individual extractable metabolites. In an attempt to identify these metabolites, two DTPA-amino acid sequences were synthesized: DTPA-D-Phe-Cys and DTPA-D-Phe. Under the conditions used for metabolite analysis, (111)In-DTPA-D-Phe-Cys-OH eluted at 14.6 min and (111)In-DTPA-D-Phe-OH eluted at 7.0 min. Each of these standard sequences was combined with the soluble portion of the organ homogenate and was shown by HPLC to coelute with the metabolites. These data suggest that (111)In-DTPA-octreotide was initially degraded to (111)In-DTPA-D-Phe-Cys-OH and (111)In-DTPA-D-Phe-OH. The (111)In-DTPA-D-Phe-Cys-OH was further degraded to (111)In-DTPA-D-Phe-OH, which appeared to be the final metabolite that was extracted from the organs. From these results, it can be concluded that at longer time points (> 2 h postinjection) a significant amount of (111)In was retained in nontarget organs as (111)In-DTPA-D-Phe-OH and (111)In-DTPA-D-Phe-Cys-OH and not as intact (111)In-DTPA-octreotide.Bioconjugate Chemistry 9(2):192-200. · 4.93 Impact Factor
