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Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 Affibody for single-photon imaging of HER2 expression in tumors
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2006 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 47, no 3, 512-519 p.Article in journal (Refereed) Published
Abstract [en]

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, HiS(6)-(ZHER(2:4))(2) (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of Tc-99m might improve the availability of the labeled conjugate, and Tc(l)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare Tc-99m-labeled Hi0S(6)-(Z(HER2:4))(2) and to evaluate its targeting properties compared with the targeting properties of I-125 -4-iodobenzoate-HiS(6)-(Z(HER2:4))(2) [I-125-HiS(6)-(Z(HER2:4))(2)]- Methods: The labeling of HiS6-(Z(HER2:4))2 with Tc-99m was performed with an IsoLink kit. The specificity of Tc-99m-HiS(6)-(Z(HER2:4))(2) binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of Tc-99m-HiS(6)-(Z(HER2,4))(2) and I-125-HiS(6)-(Z(HER2:4))(2) in tumor-bearing BALB/c nulnu mice were determined. Results: The labeling yield for Tc-99m-HIS6(Z(HER2:4))(2) was similar to 60% (50 degrees C), and the radiochernical purity was greater than 97%. The conjugate was stable during storage and under histicline and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%]A/gj) of 2.6 %IA/g for Tc-99m-HiS(6)-(Z(HER2:4))(2) and 2.3 % IA/g for I-125-HiS6-(Z(HER2:4))(2) at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. Conclusion: The use of Tc(l)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-HiS(6)-(Z(HER2:4))(2) conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with Tc-99m should be investigated further.

Place, publisher, year, edition, pages
2006. Vol. 47, no 3, 512-519 p.
Keyword [en]
Affibody, HER2, Tc(l)-carbonyl chemistry, indirect iodination, tumor targeting, breast-cancer, somatostatin analogs, c-erbb-2 expression, small peptides, tc-99m, antibody, therapy, radiopharmaceuticals, carcinoma, proteins
URN: urn:nbn:se:kth:diva-16282ISI: 000249695800022ScopusID: 2-s2.0-33645974332OAI: diva2:334324
QC 20100525Available from: 2010-08-05 Created: 2010-08-05Bibliographically approved

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