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Letters to the Editor |
and
Marco Salvatore, MD*
Dip Scienze Biomorfologiche e Funzionali, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli Federico II, via S. Pansini 5, Naples 80131, Italy*. e-mail: pace@unina.it
Istituto di Biostrutture e Bioimmagini, C.N.R., Naples, Italy
Editor:
We read with great interest the excellent review on diagnostic imaging in multiple myeloma by Dr Angtuaco and colleagues in the April 2004 issue of Radiology (1). We would like to address just a few issues related to the use of technetium 99m (99mTc) sestamibi. In the past few years, different groups have reported consistent results by using this tracer in patients with multiple myeloma (2–7). In particular, several investigators (4–6) evaluated successfully the use of 99mTc sestamibi in the follow-up of these patients. For instance, we found that all patients that had negative findings with 99mTc sestamibi imaging at follow-up were actually in remission (either complete or partial), while 86% of those that had positive findings experienced disease progression (4).
In their review article, Dr Angtuaco and colleagues (1) pointed out the limited value of 99mTc sestamibi in the follow-up evaluation due to the development of the multidrug resistant phenotype, which causes a decrease of net tracer accumulation. We agree that the enhanced outward transport of the tracer in Pgp-overexpressing tumors actually decreases the net cellular uptake of 99mTc sestamibi. It should be noted, however, that this effect is time dependent and particularly evident at 2–4 hours postinjection (8,9).
Therefore, by using an appropriate acquisition time (ie, 10 minutes after tracer injection), tracer uptake is not affected markedly by multidrug resistance. Furthermore, the washout rate of the tracer can be estimated and may be used to assess multidrug resistance in multiple myeloma, as reported for other types of tumors (9–11). Finally, we recently reported (12,13) the dependence of tracer influx from Bcl-2 overexpression and showed that malignant tumors with absolute lack of tracer uptake on early images have a defective apoptotic program and high levels of Bcl-2. These observations may have important clinical implications for patients with multiple myeloma.
REFERENCES
Department of Radiology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72212. e-mail: angtuacoedgardoj@uams.edu
We thank Dr Pace and colleagues for their comments about the role of 99mTc sestimibi imaging in multiple myeloma with regard to our recent article (1). We agree, and indeed, it is well known that early imaging (ie, at 10 minutes postinjection) can overcome the washout of the radiopharmaceutical in the setting of multidrug resistance, since visualization of isotope uptake by tumor in this immediate postinjection time frame is not affected.
However, the much higher background level at this early time adversely affects overall imaging quality. Hence, most imagers who use this radiopharmaceutical for this indication will image early and late. We thus stated in our article that lack of uptake at the delayed time frame (ie, 4 hours) should not be used alone to determine the presence or absence of tumor, since washout occurs in the setting of multidrug resistance. Interestingly, Dr Pace and colleagues also report that myeloma cells that express Bcl-2, a powerful inhibitor of tumor apoptosis that is associated with an entirely different form of drug resistance, will not accumulate the 99mTc sestimibi isotope, even in this early time frame. These phenomena help stress the importance of complementary imaging modalities, such as use of both radionuclide and magnetic resonance (MR) imaging, and correlation with laboratory findings and random and image-guided biopsy for the optimum care of patients with multiple myeloma.
Just as MR imaging is nonspecific (with effects of marrow stimulation medication, for instance, sometimes simulating the cellular infiltration due to myeloma), so is imaging with 98mTc sestimibi, and images must be interpreted in context. Since we submitted our manuscript for publication, Durie et al (2) published an excellent article on fluorodeoxyglucose (FDG) positron emission tomography (PET) of multiple myeloma. We believe that the article of Durie et al establishes FDG PET to be the standard of care for functional imaging of multiple myeloma, complementary to MR imaging and skeletal survey. Nonetheless, despite the limitations of 99mTc sestimibi, it remains a useful imaging agent for multiple myeloma, especially if FDG PET imaging is not available.
REFERENCES
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