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Evaluation of 64Cu-labeled DOTA-d-Phe1-Tyr3-octreotide (64Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors

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Abstract

Objective

In-111 (111In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 (64Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a 64Cu-labeled octreotide analog, 64Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-d-Phe1-Tyr3-octreotide (64Cu-DOTA-TOC).

Methods

64Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45°C. The stability of 64Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of 64Cu-DOTA-TOC and 111In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of 64Cu-DOTA-TOC or 64Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide (64Cu-TETA-OC). The tumor was imaged using 64Cu-DOTA-TOC, 64Cu-TETA-OC, and FDG with an animal PET scanner.

Results

64Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. 64Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of 64Cu was higher than that of 111In in all organs except kidney. In tumor-bearing mice, 64Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 ± 1.17 at 6 h after administration. 64Cu-DOTA-TOC showed significantly higher accumulation in the tumor than 64Cu-TETA-OC. 64Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of 18F-FDG PET and very similar to that of 64Cu-TETA-OC.

Conclusions

64Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.

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Acknowledgment

The authors would like to thank Sumitomo Heavy Industries Ltd., for assistance with the production of 64Cu.

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Correspondence to Hirofumi Hanaoka.

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Hanaoka, H., Tominaga, H., Yamada, K. et al. Evaluation of 64Cu-labeled DOTA-d-Phe1-Tyr3-octreotide (64Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors. Ann Nucl Med 23, 559–567 (2009). https://doi.org/10.1007/s12149-009-0274-0

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  • DOI: https://doi.org/10.1007/s12149-009-0274-0

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