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PET Tracers for Osteosarcoma

Duke University Medical Center, Durham, North Carolina

TO THE EDITOR:

Thanks to Dr. Winfried Brenner et al., and The Journal of Nuclear Medicine, for publishing the excellent continuing education article on imaging of osteosarcoma with PET (1).

I have a correction and a comment. The brief discussion of non–¹⁸F-FDG PET tracers leaves the reader with the impression that non–¹⁸F-FDG tracers have been used only in animal studies. In fact, as the title of the authors’ reference 41 implies, studies with ¹³N-labeled amino acids had been performed on patients with osteosarcoma and soft-tissue sarcomas several years before the first clinical use of ¹⁸F-FDG in these tumors. Studies using ¹³N-(L)-glutamate included pretherapy planar imaging studies (2,3) and quantitative follow-up studies that correlated the histologic extent of residual viable tumor with changes in ¹³N uptake (4). A review published in 1984 included PET images of ¹³N-(L)-glutamate and ¹⁸F-sodium fluoride in osteosarcoma (5).

The use of amino acids natively labeled with short-lived positron emitters offered several advantages to the pediatric patient population, including rapid enzymatic synthesis, rapid tumor localization (minutes as opposed to hours with ¹⁸F-FDG), and very low radiation exposure. Unfortunately, the early enthusiasm for ¹³N and ¹¹C tracers was soon dampened because of the scarcity of hospital-based cyclotrons. If PET scanners and on-site production facilities continue to proliferate, perhaps a place will be found for non–¹⁸F-FDG PET tracers for osteosarcoma.

REFERENCES

1. Brenner W, Bohuslavizky KH, Eary JF. PET imaging of osteosarcoma. J Nucl Med. 2003;44:930–942.[Abstract/Free Full Text]
2. Gelbard AS, Benua RS, Laughlin JS, Rosen G, Reiman RE, McDonald JM. Quantitative scanning of osteogenic sarcoma with nitrogen-13 labeled L-glutamate. J Nucl Med. 1979;20:782–784.[Abstract/Free Full Text]
3. Reiman RE, Rosen G, Gelbard AS, Benua RS, Laughlin JS. Imaging of primary Ewing sarcoma with N-13 L-glutamate. Radiology. 1982;142:495–500.[Abstract/Free Full Text]
4. Reiman RE, Huvos AG, Benua RS, Rosen G, Gelbard AS, Laughlin JS. Quotient imaging with N-13 L-glutamate in osteogenic sarcoma: correlation with tumor viability. Cancer. 1981;48:1976–1981.[Medline]
5. Reiman RE, Rosen G, Gelbard AS, Benua RS, Yeh SDJ, Laughlin JS. Diagnostic demands in clinical and experimental oncology: application of substrates labeled with positron-emitting radionuclides. In: Knapp WH, Vyska K, eds. Current Topics in Tumor Cell Physiology and Positron-Emission Tomography. Berlin, Germany: Springer-Verlag; 1984:73–85.

University of Washington Medical Center, Seattle, Washington
University Hospital Hamburg, Eppendorf, Germany

REPLY:

We appreciate the comments and additional information provided by Dr. Reiman regarding our review article on PET imaging of osteosarcoma (1).

When searching PubMed, the online service of the National Library of Medicine, for PET tracers besides ¹⁸F-FDG and ¹⁸F-fluoride ion (¹⁸F) that have been applied to osteosarcoma, we retrieved experimental studies using ¹⁸F-labeled monoclonal antibodies (2), ¹⁸F-fluoromisonidazole (3), ¹⁸F-labeled Arg-Gly-Asp (RGD)–containing glycopeptide (4,5), ³H-thymidine (3), and PETimaging of p53 transcriptional activity (6). Although we used various search terms on PubMed, the study by Sordillo et al. (7) was the only patient study we found, and the studies mentioned by Dr. Reiman did not surface. Thus, we are grateful for this information on human studies with ¹³N-(L)-glutamate—information that gives us a more complete overview of PET imaging of osteosarcoma.

We also would like to use Dr. Reiman’s comments on successful sarcoma imaging with ¹³N- and ¹¹C-labeled compounds to encourage the application of non–¹⁸F-FDG PET tracers. When PET scanners with on-site cyclotron facilities become more ubiquitous and shipping of ¹⁸F-labeled compounds to satellite PET devices is available, both new and "old" tracers should be applied in patient studies to investigate their potential for individualized risk evaluation. The use of a PET tracer such as ¹³N-(L)-glutamate, ¹³N-methionine, ¹⁸F-fluorothymidine, ¹¹C-acetate, ¹¹C-verapamil, ¹⁸F-misonidazole, or ¹⁸F-annexin, to name just a few, could give detailed insight into biologic features such as amino acid metabolism, cell proliferation, multidrug resistance 1–induced chemotherapy resistance, tumor hypoxia, and apoptosis. This additional information will assist physicians in choosing the best available therapy for an individual patient and in tailoring follow-up to the specific case. Such an individualized approach will further improve patient outcome and will also allow knowledge of molecular imaging to be applied clinically and help nuclear medicine continue to evolve as a modern specialty in the fast-growing field of sophisticated diagnostic procedures.

REFERENCES

1. Brenner W, Bohuslavizki KH, Eary JF. PET imaging of osteosarcoma. J Nucl Med. 2003;44:930–942.
2. Page RL, Garg PK, Garg S, et al. PET imaging of osteosarcoma in dogs using a fluorine-18-labeled monoclonal antibody Fab fragment. J Nucl Med. 1994;35:1506–1513.[Abstract/Free Full Text]
3. Rasey JS, Koh WJ, Grierson JR, Grunbaum Z, Krohn KA. Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia. Int J Radiat Oncol Biol Phys. 1989;17:985–991.[Medline]
4. Haubner R, Wester HJ, Burkhart F, et al. Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J Nucl Med. 2001;42:326–336.[Abstract/Free Full Text]
5. Haubner R, Wester HJ, Weber WA, et al. Noninvasive imaging of alpha(v)beta3 integrin expression using ¹⁸F-labeled RGD-containing glycopeptide and positron emission tomography. Cancer Res. 2001;61:1781–1785.[Abstract/Free Full Text]
6. Doubrovin M, Ponomarev V, Beresten T, et al. Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo. Proc Natl Acad Sci USA. 2001;98:9300–9305.[Abstract/Free Full Text]
7. Sordillo PP, Benua RS, Gelbard AS, et al. Imaging of human tumors and organs with N-13-labeled L-methionine. Am J Physiol Imaging. 1986;1:195–200.[Medline]

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