Molecular Imaging for Breast Cancer Phenotyping: Tc-99m sestamibi Scintigraphy cannot be Missed

Sir,

We read with great interest the paper titled “Role of ^99mTc-sestamibi scintimammography in predicting response to neoadjuvant chemotherapy (NACT) in locally advanced breast cancer (LABC): A prospective study” by Moulika et al.[1] in the Indian Journal of Nuclear Medicine. The study involved 34 patients with LABC who underwent scintigraphy with ^99mTc-sestamibi before NACT. Parameters such as wash-out-rate (WOR) and tumor-to-normal breast ratio (T/B) were calculated based on early and late images, serving as surrogate biomarkers for P-glycoprotein (PgP) expression, which is associated with chemoresistance. The study found a negative correlation between WOR and the percentage decrease in tumor size, indicating higher PgP expression may lead to reduced response to chemotherapy. Conversely, a positive correlation was found between T/B buildup and the percentage decrease in tumor size, suggesting potential predictive value for this parameter in assessing response to NACT.

We praise the authors for their intriguing research, warranting further discussion. Over the past two decades, personalized medicine has emerged, recognizing that not all medications work equally for all patients. Instead, each person should be seen as a unique entity with distinct genetic, molecular, and environmental traits. Treatment strategies should be tailored to meet each patient’s specific needs. Molecular imaging, especially using nuclear medicine techniques such as positron emission tomography/computed tomography (PET/CT), provides valuable insights into tumor biology. PET/CT offers a wide range of radiopharmaceuticals, including ¹⁸F-fludeoxyglucose (FDG), which can preliminarily assess breast cancer characteristics. Studies show that less aggressive phenotypes have lower ¹⁸F-FDG uptake compared to more aggressive tumors. In addition, ¹⁸F-Fluoro-17β-Estradiol has recently been endorsed by the National Comprehensive Cancer Network as an in vivo imaging modality for identifying and quantifying estrogen receptor (ER), predicting response to ER-targeted therapy, and monitoring ER status to promptly detect acquired resistance.[2] Ultimately, a radiolabeled affibody, specifically ⁶⁸Ga-ABY-025, has been synthesized and effectively utilized for detecting human epidermal growth factor receptor 2 (HER2) status in breast cancer patients. This approach has yielded promising preliminary results, offering the potential for prognostic stratification before initiating HER2-targeted therapy.[3]

In this scenario, none of the aforementioned PET-based radiopharmaceuticals can provide equivalent information to that obtained with ^99mTc-sestamibi, which is indispensable for characterizing PgP-status in breast cancer before NACT. Indeed, it must be emphasized that PET/CT stands out in comparison to scintigraphy due to its superior spatial resolution and ability to provide accurate quantitative parameters. In this regard, in the paper by Moulika et al., the authors did not perform single-photon emission CT (SPECT/CT), which has been shown to significantly improve diagnostic accuracy compared to planar images alone.[4] This topic should be the focus of future investigations. However, SPECT still remains the most affordable and widespread nuclear medicine modality worldwide, with its own intrinsic value. From this perspective, further studies are needed to better define the role of various molecular imaging probes in the workup for the in vivo phenotyping of breast cancer, without overlooking the potential of each technological approach [Figure 1].

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Figure 1 Schematic representation of the main positron emission tomography and gamma-camera/single-photon emission computed tomography tracers employed for breast cancer phenotyping. PET: Positron emission tomography, SPECT: Single-photon emission computed tomography, ER: Estrogen receptor

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