Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer

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Abstract

Purpose

Positron emission tomography using 3′-deoxy-3′-[ ¹⁸F]fluorothymidine ([ ¹⁸F]FLT) has been suggested as a means for monitoring response to chemotherapy. The aim of this study was to evaluate the validity of simplified uptake measures for assessing response to chemotherapy using [ ¹⁸F]FLT in locally advanced breast cancer (LABC).

Procedures

Fifteen LABC patients underwent dynamic [ ¹⁸F]FLT scans both prior to and after the first cycle of chemotherapy with fluorouracil, epirubicin or doxorubicin, and cyclophosphamide. The net uptake rate constant of [ ¹⁸F]FLT, K _i, determined by non-linear regression (NLR) of an irreversible two-tissue compartment model was used as the gold standard. In addition to Patlak graphical analysis, standardised uptake values (SUV) and tumour-to-whole blood ratio (TBR) were used for analysing [ ¹⁸F]FLT data. Correlations and relationships between simplified uptake measures and NLR before and after chemotherapy were assessed using regression analysis.

Results

No significant differences in both pre- and post-chemotherapy relationships between any of the simplified uptake measures and NLR were found. However, changes in SUV between baseline and post-therapy scans showed a significant negative bias and slope less than one, while TBR did not.

Conclusions

In LABC, TBR instead of SUV may be preferred for monitoring response to chemotherapy with [ ¹⁸F]FLT.

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Most cited references 18

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Imaging early changes in proliferation at 1 week post chemotherapy: a pilot study in breast cancer patients with 3'-deoxy-3'-[18F]fluorothymidine positron emission tomography.

A Nahhas, Eric Aboagye, David M Vigushin … (2007)

3'-deoxy-3'-[18F]fluorothymidine positron emission tomography ([18F]FLT-PET) has been developed for imaging cell proliferation and findings correlate strongly with the Ki-67 labelling index in breast cancer. The aims of this pilot study were to define objective criteria for [18F]FLT response and to examine whether [18F]FLT-PET can be used to quantify early response of breast cancer to chemotherapy. Seventeen discrete lesions in 13 patients with stage II-IV breast cancer were scanned prior to and at 1 week after treatment with combination 5-fluorouracil, epirubicin and cyclophosphamide (FEC) chemotherapy. The uptake at 90 min (SUV90) and irreversible trapping (Ki) of [18F]FLT were calculated for each tumour. The reproducibility of [18F]FLT-PET was determined in nine discrete lesions from eight patients who were scanned twice before chemotherapy. Clinical response was assessed at 60 days after commencing FEC. All tumours showed [18F]FLT uptake and this was reproducible in serial measurements (SD of mean % difference=10.5% and 15.1%, for SUV90 and Ki, respectively; test-retest correlation coefficient>or=0.97). Six patients had a significant clinical response (complete or partial) at day 60; these patients also had a significant reduction in [18F]FLT uptake at 1 week. Decreases in Ki and SUV90 at 1 week discriminated between clinical response and stable disease (p=0.022 for both parameters). In three patients with multiple lesions there was a mixed [18F]FLT response in primary tumours and metastases. [18F]FLT response generally preceded tumour size changes. [18F]FLT-PET can detect changes in breast cancer proliferation at 1 week after FEC chemotherapy.

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In vivo validation of 3'deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) as a proliferation imaging tracer in humans: correlation of [(18)F]FLT uptake by positron emission tomography with Ki-67 immunohistochemistry and flow cytometry in human lung tumors.

Hubert Vesselle, D. Wood, Erwin R. Schmidt … (2002)

Tumor proliferation has prognostic value in resected early stage non-small cell lung cancer (NSCLC) and can, therefore, predict which NSCLCs are at high risk for recurrence after resection and would benefit from additional therapy. It may also predict which tumor will respond to cell cycle-targeted chemotherapy and help assess the tumor response, besides helping to differentiate benign from malignant lung lesions. We evaluated whether the uptake of the new positron emission tomography (PET) tracer 3'deoxy-3'-[18F]fluorothymidine (FLT) in a series of suspected NSCLCs correlated with tumor proliferation assessed by Ki-67 immunohistochemistry and flow cytometry. Ten patients with 11 biopsy-proven or clinically suspected NSCLC underwent 2-h dynamic PET imaging after i.v. injection of 0.07 mCi/kg FLT. Tumor FLT uptake was quantitated with the maximum pixel standardized uptake value (maxSUV), the partial volume corrected maxSUV (PV-corr-maxSUV), the average SUV over a small region-of-interest (aveSUV) and with Patlak analysis of FLT flux (aveFLTflux). The lesion diameter from computed tomography was used to correct the maxSUV for PV effects using recovery coefficients determined for the General Electric Advance PET scanner. Two of the 11 lesions were benign inflammatory lesions and 9 were NSCLCs. Immunohistochemistry for Ki-67 (proliferation index marker) was performed on all 11 tissue specimens (10 resections, 1 NSCLC percutaneous biopsy), and the S-phase fraction (SPF) from flow cytometry could be determined for 10. The specimens were reviewed for histology and cellular differentiation (poor, moderate, well). Lesions ranged from 1.6 to 7.7 cm. Excellent correlations were found between SUV measures of FLT uptake and Ki-67 scores [percentage of positive cells; maxSUV versus Ki-67: Rho = 0.78, P = 0.0043 (n = 11); PV-corr-maxSUV versus Ki-67: Rho = 0.83, P = 0.0028 (n = 10); aveSUV versus Ki-67: Rho = 0.84, P = 0.0011 (n = 11)]. Correlation between Ki-67 proliferation scores and Patlak measures of FLT uptake were also strong: aveFLTflux versus Ki-67: Rho = 0.94, P < 0.0001 (n = 11). The correlation between the SPF and all indices of FLT uptake was weaker and reached statistical significance for only two uptake indices [maxSUV versus SPF: Rho = 0.69, P = 0.03 (n = 10); PV-corr-maxSUV versus SPF: Rho = 0.36, P = 0.35 (n = 9); aveSUV versus SPF: Rho = 0.67, P = 0.03 (n = 10); aveFLTflux versus SPF: Rho = 0.46, P = 0.18 (n = 10)]. FLT PET may be used to noninvasively assess proliferation rates of lung masses in vivo. Therefore, FLT PET may play a significant role in the evaluation of indeterminate pulmonary lesions, in the prognostic assessment of resectable NSCLC, and possibly in the evaluation of NSCLC response to chemotherapy.

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Monitoring response to therapy in cancer using [18F]-2-fluoro-2-deoxy-D-glucose and positron emission tomography: an overview of different analytical methods.

I Paglianiti, Adriaan Lammertsma, Pieter J. Hoekstra … (2000)

[18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) is considered a valuable tool in the diagnosis and staging of cancer. In addition, it seems promising as a technique to monitor response to therapy. Progress is hampered, however, by the fact that various methods for the analysis of uptake of FDG in tumours have been described and that it is by no means clear whether these methods have the same sensitivity for monitoring response to treatment. As interest in monitoring response using FDG PET is growing, the danger exists that non-optimal methods will be used for evaluation. Hence an overview of the various analytical methods is given, highlighting both advantages and shortcomings of each of the methods. The ideal analytical method for response monitoring should represent an optimal trade-off between accuracy and simplicity (clinical applicability). At present, that trade-off still needs to be defined. Studies relating response, as measured with any of the available analytical methods, to outcome are urgently needed. Until then response monitoring studies should be conducted in such a way that all analytical methods can be compared with the most quantitative one, which at present is full compartmental modelling of the data.

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Author and article information

Contributors

: +46-18-6119644 , mark.lubberink@radiol.uu.se

Journal

Journal ID (nlm-ta): Mol Imaging Biol

Journal ID (iso-abbrev): Mol Imaging Biol

Title: Molecular Imaging and Biology

Publisher: Springer-Verlag (New York )

ISSN (Print): 1536-1632

ISSN (Electronic): 1860-2002

Publication date (Electronic): 6 March 2012

Publication date PMC-release: 6 March 2012

Publication date (Print): December 2012

Volume: 14

Issue: 6

Pages: 777-782

Affiliations

[1 ]Department of Nuclear Medicine & PET Research, VU University Medical Centre, Amsterdam, The Netherlands

[2 ]Nuclear Medicine & PET, Uppsala University, Uppsala, Sweden

[3 ]Department of Medical Oncology, Medical Centre Alkmaar, Alkmaar, The Netherlands

[4 ]Netherlands Cancer Institute, Amsterdam, The Netherlands

[5 ]PET Centre, Uppsala University Hospital, 751 85 Uppsala, Sweden

Article

Publisher ID: 547

DOI: 10.1007/s11307-012-0547-1

PMC ID: 3492702

PubMed ID: 22392642

SO-VID: 17b5fb96-96f0-47ea-ac15-dc5558b8ecc8

History

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ScienceOpen disciplines: Molecular biology

Keywords: pet,flt,suv,modelling,response monitoring

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ScienceOpen disciplines: Molecular biology

Keywords: pet, flt, suv, modelling, response monitoring

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