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Comparative Study
. 2006 May;47(5):793-6.

Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET

Peter M Smith-Jones  1 , David Solit, Farzana Afroze, Neal Rosen, Steven M Larson
Affiliations
Comparative Study

Early tumor response to Hsp90 therapy using HER2 PET: comparison with 18F-FDG PET

Peter M Smith-Jones et al. J Nucl Med. 2006 May.

Abstract

We compared (68)Ga-DOTA-F(ab')(2)-herceptin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid [HER2 PET]) and (18)F-FDG PET for imaging of tumor response to the heat shock protein 90 (Hsp90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17AAG).

Methods: Mice bearing BT474 breast tumor xenografts were scanned with (18)F-FDG PET and HER2 PET before and after 17AAG treatment and then biweekly for up to 3 wk.

Results: Within 24 h after treatment, a significant decrease in HER2 was measured by HER2 PET, whereas (18)F-FDG PET uptake, a measure of glycolysis, was unchanged. Marked growth inhibition occurred in treated tumors but became evident only by 11 d after treatment. Thus, Her2 downregulation occurs independently of changes in glycolysis after 17AAG therapy, and Her2 reduction more accurately predicts subsequent tumor growth inhibition.

Conclusion: HER2 PET is an earlier predictor of tumor response to 17AAG therapy than (18)F-FDG PET.

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Figures

Figure 1
Figure 1
(A) Comparison of body mass of nude mice treated with 17AAG vs. control animals. Animals were treated with 3 × 50 mg/kg 17AAG over 24 h on day 0. (B) Comparison of BT474 tumor growth in nude mice treated with 17AAG vs. control animals.
Figure 2
Figure 2
Comparison of 68Ga-DOTA-F(ab′)2-herceptin uptake in nude mice with BT474 tumors before and after 17AAG treatment. Animals were treated with 3 × 50 mg/kg of 17AAG over 24 h on day 0 and data are normalized to day –2 uptake.
Figure 3
Figure 3
microPET images (coronal slice and transverse slice through tumor) of 68Ga-DOTA-F(ab′)2-herceptin uptake in the same mouse with a BT474 tumor at –2 d (A), 1 d (B), 5 d (C), 8 d (D), and 12 d (E) after treatment with 3 × 50 mg/kg of 17AAG over 24 h on day 0. Arrows indicate tumor.
Figure 4
Figure 4
Comparison of 18F-FDG uptake in nude mice with BT474 tumors before and after 17AAG treatment. Animals were treated with 3 × 50 mg/kg of 17AAG over 24 h on day 0 and data are normalized to day –6 uptake.
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References

    1. Smith-Jones PM, Solit DB, Akhurst T, Afroze F, Rosen N, Larson SM. Imaging the pharmacodynamics of HER2 degradation in response to Hsp90 inhibitors. Nat Biotechnol. 2004;22:701–706. - PubMed
    1. Czernin J. Clinical applications of FDG-PET in oncology. Acta Med Austriaca. 2002;29:162–170. - PubMed
    1. Kumar R, Alavi A. Fluorodeoxyglucose-PET in the management of breast cancer. Radiol Clin North Am. 2004;42:1113–1122. - PubMed
    1. Avril NE, Weber WA. Monitoring response to treatment in patients utilizing PET. Radiol Clin North Am. 2005;43:189–204. - PubMed
    1. Yao M, Graham MM, Smith RB, et al. Value of FDG PET in assessment of treatment response and surveillance in head-and-neck cancer patients after intensity modulated radiation treatment: a preliminary report. Int J Radiat Oncol Biol Phys. 2004;60:1410–1418. - PubMed

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