Correspondence

Positron-Emission Tomography in Cancer Therapy

N Engl J Med 2006; 354:1958-1960May 4, 2006

Article

To the Editor:

The excellent review by Juweid and Cheson (Feb. 2 issue)1 on the powerful diagnostic use of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) as a tracer for hypermetabolic neoplasms raises interesting questions about its potential use as a therapeutic agent. Other tumor-avid radiopharmaceutical agents such as ⁹⁰Y- or ¹³¹I-labeled B-cell antibodies can produce regression of lymphoma when given in therapeutic doses,2 and a potential exists for the same approach with tumor-avid positron-emitting compounds such as ¹⁸F-FDG. The initial basic-science work from the early 1980s demonstrated the diagnostic potential of ¹⁸F-FDG for the detection of cancer,3 and there is later evidence that direct intratumoral injection of the same tracer into small gliomas transplanted into nude mice can have a radiotherapeutic effect and influence tumor growth.4 Further research into the use of tumor-avid positron-emitting compounds might be able to help advance both the diagnostic and the radiotherapeutic aspects of oncology.5

Michael A. Meyer, M.D.
Jacobs Neurological Institute, Buffalo, NY 14203
michaelandrewmeyer@yahoo.com

5 References

1
Juweid ME, Cheson BD. Positron-emission tomography and assessment of cancer therapy. N Engl J Med 2006;354:496-507
Full Text | Web of Science | Medline

2
Juweid ME. Radioimmunotherapy of B-cell non-Hodgkin's lymphoma: from clinical trials to clinical practice. J Nucl Med 2002;43:1507-1529
Web of Science | Medline

3
Som P, Yonekura Y, Oster ZH, et al. Quantitative autoradiography with radiopharmaceuticals. Part 2. Applications in radiopharmaceutical research: concise communication. J Nucl Med 1983;24:238-244
Web of Science | Medline

4
Meyer MA, Caday CG, Han Y, Vickers B, Nanda A. Potential radiotherapy of human gliomas with 18F-fluorodeoxyglucose (18F-FDG). Soc Neurosci Abstr 1996;22:948-948

5
Meyer MA. Radiotherapeutic use of 2-deoxy-2-[18F]fluoro-D-glucose -- a comment. Breast Cancer Res 2004;6:E2-E2
CrossRef | Web of Science | Medline

To the Editor:

In their thorough review, Juweid and Cheson did not mention the role of positron-emission tomography (PET) in the assessment of targeted therapy for gastrointestinal stromal tumors. In this setting, dimensional criteria are not always appropriate instruments of evaluation.1 Imatinib is beneficial in 85 percent of patients, but in the first months of therapy, up to 75 percent of the patients have disease that appears to remain stable. Even initially increasing lesions can be responsive ones. PET usually depicts this kind of response better than computed tomography (CT) (accuracy at one month, 85 percent vs. 44 percent).2 PET has been recommended as a more “definitive” way to assess response in gastrointestinal stromal tumors.3 PET is also better than CT in predicting early response to imatinib,4 which is associated with longer progression-free survival.5 Better prediction helps identify patients without a response, so they can receive second-line targeted therapy earlier, and it can reduce unnecessary and expensive therapy.

Sandra Aliberti, M.D.
Giovanni Grignani, M.D.
Massimo Aglietta, M.D.
Institute for Cancer Research and Treatment, 10060 Candiolo, Italy
ggrignani@ircc.mauriziano.it

5 References

1
Choi H, Charnsangavej C, de Castro Faria S, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol 2004;183:1619-1628
Web of Science | Medline

2
Antoch G, Kanja J, Bauer S, et al. Comparison of PET, CT and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 2004;45:357-365
Web of Science | Medline

3
Demetri GD, Benjamin R, Blanke CD, et al. NCCN task force report: optimal management of patients with gastrointestinal stromal tumor (GIST) -- expansion and update of NCCN clinical practice guidelines. J Natl Compr Cancer Net 2004;2:Suppl 1:S1-S26
Medline

4
Gayed I, Vu T, Iyer R, et al. The role of ¹⁸F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. J Nucl Med 2004;45:17-21[Erratum, J Nucl Med 2004;45:1803.]
Web of Science | Medline

5
Stroobants S, Goeminne J, Seegers M, et al. 18FDG-positron emission tomography for early prediction of response in advanced soft tissue sarcoma treated with imatinib mesylate (Glivec). Eur J Cancer 2003;39:2012-2020
CrossRef | Web of Science | Medline

Author/Editor Response

The issue raised by Meyer regarding the potential use of ¹⁸F-FDG as a therapeutic agent is intriguing. Unfortunately, this approach may not be very practical for systemic therapy in most FDG-avid cancers, because extremely high doses of ¹⁸F-FDG need to be administered to achieve even modest tumoricidal effects. For example, about 4800 mCi of ¹⁸F-FDG must be given to achieve a tumor radiation dose of only 1100 cGy in a breast-cancer metastasis with moderate ¹⁸F-FDG uptake.1 Although such doses of ¹⁸F-FDG are likely to be tolerated, a substantial amount of radiation is delivered to normal organs, particularly the brain, kidneys, and bladder, for the relatively low tumor dose delivered. The expectedly high exposure to radiation of health personnel involved in administering such a treatment (caused by the 511 keV photons) and the requirement for an on-site cyclotron to produce large quantities of ¹⁸F-FDG are likely to make this approach impractical. Intratumoral injection of ¹⁸F-FDG for treatment of localized tumors, such as gliomas, is interesting but may also have these problems. Other positron emitters with a longer physical half-life than fluorine-18, such as copper-64, can be used to label a variety of cancer-specific compounds, such as peptides or antibodies.2 Such agents may hold greater promise.

Aliberti and colleagues raise an important point about the use of PET for assessment of targeted therapy in patients with gastrointestinal stromal tumors. We agree that PET generally provides earlier and more accurate assessment of response to imatinib and probably other targeted therapies than does conventional imaging. This advantage is perhaps most significant in patients with potentially resectable tumors who undergo neoadjuvant imatinib therapy in hopes of improving resectability.3 Finally, as shown by Antoch et al.,4 functional–anatomical assessment with dual-modality PET–CT is likely to be even more accurate than PET alone for assessment of response to imatinib and, if the CT portion is performed with intravenous contrast medium, may become the preferred imaging method for staging and restaging of this disease, but first this needs to be demonstrated in larger prospective studies.

Malik E. Juweid, M.D.
University of Iowa, Iowa City, IA 52242
malik-juweid@uiowa.edu

Bruce D. Cheson, M.D.
Georgetown University Hospital, Washington, DC 20007

4 References

1
Moadel RM, Nguyen AV, Lin EY, et al. Positron emission tomography agent 2-deoxy-2-[18F]-fluoro-D-glucose has a therapeutic potential in breast cancer. Breast Cancer Res 2003;5:R199-R205
CrossRef | Web of Science | Medline

2
Connett JM, Anderson CJ, Guo L-W, et al. Radioimmunotherapy with a 64Cu-labeled monoclonal antibody: a comparison with 67Cu. Proc Natl Acad Sci U S A 1996;93:6814-6818
CrossRef | Web of Science | Medline

3
Demetri GD, Benjamin R, Blanke CD, et al. NCCN task force report: optimal management of patients with gastrointestinal stromal tumor (GIST) -- expansion and update of NCCN clinical practice guidelines. J Natl Compr Cancer Net 2004;2:Suppl 1:S1-S26
Medline

4
Antoch G, Kanja J, Bauer S, et al. Comparison of PET, CT and dual-modality PET/CT imaging for monitoring of imatinib (STI571) therapy in patients with gastrointestinal stromal tumors. J Nucl Med 2004;45:357-365
Web of Science | Medline

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