Scanning and imaging developments

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J Nucl Med. (javascript:AL_get(this,%20'jour',%20'J%20Nucl%20M ed.');) 2009 Oct;50(10):1598-604. Epub 2009 Sep 16.
Functional images reflect aggressiveness of endometrial carcinoma: estrogen receptor expression combined with 18F-FDG PET.

Tsujikawa T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tsujikawa%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Yoshida Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Yoshida%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kudo T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kudo%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kiyono Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kiyono%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kurokawa T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kurokawa%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kobayashi M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kobayashi%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Tsuchida T (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Tsuchida%20T%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Fujibayashi Y (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Fujibayashi%20Y%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Kotsuji F (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Kotsuji%20F%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Okazawa H (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Okazawa%20H%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Biomedical Imaging Research Center, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Comment in:


J Nucl Med. 2009 Oct;50(10):1567-9. (http://www.ncbi.nlm.nih.gov/pubmed/19759107?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed _ResultsPanel.Pubmed_RVAbstract)

The grade of histologic differentiation is one of the most important prognostic factors in patients with endometrial carcinoma and postoperative staging. The aim of this study was to investigate whether 16alpha-(18)F-fluoro-17beta-estradiol ((18)F-FES) and (18)F-FDG PET reflect clinicopathologic features in patients with endometrial tumors. METHODS: A total of 22 patients with endometrial adenocarcinoma and 9 with endometrial hyperplasia (mean age, 56.0 +/- 15.3 y) underwent (18)F-FES PET for estrogen receptor imaging and (18)F-FDG PET. Regional values of tracer uptake were evaluated using standardized uptake value (SUV) and the SUV ratio of (18)F-FDG to (18)F-FES. The accuracy for predicting tumor aggressiveness defined as high-risk carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage >or= Ic or histologic grade >or= 2), low-risk carcinoma (FIGO stage <or= Ib and grade 1), and hyperplasia was compared for each PET parameter using receiver-operating-characteristic (ROC) analysis. The diagnostic accuracy of MRI findings for clinical staging was also compared. RESULTS: Although the SUV for (18)F-FDG was significantly lower in endometrial hyperplasia than in carcinoma, a significant difference between high-risk and low-risk carcinoma was observed only in SUV for (18)F-FES. High-risk carcinoma showed a significantly greater (18)F-FDG-to-(18)F-FES ratio (3.6 +/- 2.1) than did low-risk carcinoma (1.3 +/- 0.5, P < 0.01) and hyperplasia (0.3 +/- 0.1, P < 0.005). Low-risk carcinoma showed a significantly higher (18)F-FDG-to-(18)F-FES ratio than hyperplasia (P < 0.0001). In ROC analysis, the most accurate diagnostic PET parameter for predicting high-risk and low-risk carcinoma was the (18)F-FDG-to-(18)F-FES ratio. The optimal (18)F-FDG/(18)F-FES cutoff value of 2.0, determined by ROC analysis, revealed 73% sensitivity, 100% specificity, and 86% accuracy, which was better than the 77% accuracy for MRI. The (18)F-FDG-to-(18)F-FES ratio of 0.5 yielded a correct diagnosis for carcinoma from hyperplasia with 100% accuracy. CONCLUSION: Endometrial carcinoma reduces estrogen dependency with accelerated glucose metabolism as it progresses to a higher stage or grade. (18)F-FES and (18)F-FDG PET studies provide a new index of the (18)F-FDG-to-(18)F-FES ratio, which is considered the most informative index reflecting tumor aggressiveness. This index will be useful for making noninvasive diagnoses and deciding the appropriate therapeutic strategy for patients with endometrial carcinoma.

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Journal of Nuclear Medicine Vol. 50 No. 11 1848-1856
© 2009 by Society of Nuclear Medicine (http://jnm.snmjournals.org/misc/terms.shtml)
doi: 10.2967/jnumed.109.067231
<table cellpadding="0" cellspacing="0"><tbody><tr><td><hr size="1" noshade="noshade">Basic Science Investigation



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¹⁸F-FDG Small-Animal PET/CT Differentiates Trastuzumab-Responsive from Unresponsive Human Breast Cancer Xenografts in Athymic Mice

<nobr>Kristin McLarty¹</nobr>, <nobr>Aisha Fasih¹</nobr>, <nobr>Deborah A. Scollard¹</nobr>, <nobr>Susan J. Done²^,3</nobr>, <nobr>Douglass C. Vines⁴^,5</nobr>, <nobr>David E. Green⁴</nobr>, <nobr>Danny L. Costantini¹</nobr> and <nobr>Raymond M. Reilly¹^,6^,7</nobr>

¹ Department of Pharmaceutical Sciences, University of Toronto, Toronto, Ontario, Canada; ² Department of Medical Biophysics and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; ³ Ontario Cancer Institute and Department of Pathology, University Health Network, Toronto, Ontario, Canada; ⁴ Radiation Medicine Program, STTARR Innovation Centre, Princess Margaret Hospital, Toronto, Ontario, Canada; ⁵ Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; ⁶ Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; and ⁷ Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
Correspondence: For correspondence or reprints contact: Raymond M. Reilly, Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College St., Toronto, ON, Canada M5S 3M2. E-mail: raymond.reilly@utoronto.ca<script type="text/javascript"><!-- var u = "raymond.reilly", d = "utoronto.ca"; document.getElementById("em0").innerHTML = '<a href="mailto:' + u + '@' + d + '">' + u + '@' + d + '<\/a>'//--></script>
<!-- ABS -->Breast cancers (BCs) with high human epidermal growth factorreceptor type 2 (HER2) expression are most likely to respondto trastuzumab; however, the mechanisms of action of trastuzumabare complex and there are no established biomarkers to accuratelymonitor treatment outcome in individual patients. Therefore,our aim was to determine, in human BC xenografts in athymicmice treated with trastuzumab, whether there were any changesin ¹⁸F-FDG uptake that were associated with response to thedrug and that could have utility in monitoring response in patients.Methods: Baseline tumor uptake of ¹⁸F-FDG was measured in micewith MDA-MB-361 HER2-overexpressing xenografts and MDA-MB-231xenografts with low HER2 expression by small-animal PET imagingon day 0. Mice were treated with phosphate-buffered saline (PBS)or trastuzumab (4 mg/kg), and small-animal PET was repeated2 d after treatment. Maintenance doses of trastuzumab (2 mg/kg)or PBS were administered on days 7 and 14, and mice were imagedagain on days 9 and 16. Tumor uptake was measured as percentageinjected dose per gram (%ID/g) by volume-of-interest analysison days 0 (baseline), 2, 9, and 16, followed by biodistributionstudies on day 16. Tumor growth was measured, and a tumor growthindex was calculated. Results: The treatment of mice with trastuzumab,compared with control mice treated with PBS, resulted in a significantdecrease in tumor uptake of ¹⁸F-FDG in HER2-overexpressing MDA-MB-361xenografts after 16 d of treatment (2.6 ± 0.8 %ID/g vs.4.6 ± 1.8 %ID/g, respectively; P < 0.03) but not after2 or 9 d of treatment (P = 0.28–0.32). In contrast, therewas no significant change in the tumor uptake of MDA-MB-231xenografts with low HER2 expression during the entire courseof therapy (4.4 ± 1.7 %ID/g vs. 3.6 ± 1.1 %ID/g,respectively; P = 0.31). Trastuzumab treatment, compared withPBS treatment of controls, resulted in significant growth inhibitionof MDA-MB-361 xenografts as early as 10 d from the initiationof treatment (tumor growth index, 0.7 ± 0.2 vs. 1.7 ±0.3, respectively; P < 0.0005), whereas no tumor growth inhibitionwas observed for MDA-MB-231 xenografts (5.3 ± 2.7 and5.2 ± 3.0; P = 0.95). Conclusion: Changes in the tumoruptake of ¹⁸F-FDG after therapy accurately identified respondingand nonresponding human BC xenografts in athymic mice treatedwith trastuzumab; however, diminished glucose utilization didnot precede changes in tumor volume.

Key Words: HER2 • trastuzumab • ¹⁸F-FDG • PET • tumor response
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