Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers

Urbano, Nicoletta; Scimeca, Manuel; Russo, Carmela Di; Bonanno, Elena; Schillaci, Orazio

doi:10.3390/jcm9030747

Cited by 7 publications

(7 citation statements)

References 33 publications

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“…In the future, these protocols could be used to develop diagnostic investigations based on nuclear medicine studies. In our previous study, we used similar approaches to find possible in vivo imaging markers to discriminate the breast cancer characterized by the presence of BOLCs and microcalcifications to those without them [34,35].…”

Section: Discussionmentioning

confidence: 99%

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

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This study aims to investigate the possible different roles of the BMP-2 variants, cytoplasmic and nuclear variant, in both epithelial to mesenchymal transition and in microcalcifications origin in human breast cancers. To this end, the in situ expression of cytoplasmic and nuclear BMP-2 was associated with the expression of the main epithelial to mesenchymal transition biomarkers (e-cadherin and vimentin) and molecules involved in bone metabolisms (RUNX2, RANKL, SDF-1) by immunohistochemistry. In addition, the expression of cytoplasmic and nuclear BMP-2 was associated with the presence of microcalcifications. Our data showed a significant association among the number of cytoplasmic BMP-2-positive cells and the number of both vimentin (positive association) and e-cadherin (negative association) positive breast cells. Conversely, no associations were found concerning the nuclear BMP-2-positive breast cells. Surprisingly, the opposite result was obtained by analyzing the variants of BMP-2 and both the expression of RANKL and SDF-1 and the presence of microcalcifications. Specifically, the presence of microcalcifications was related to the expression of nuclear BMP-2 variant rather than the cytoplasmic one, as well as a strong association between the number of nuclear BMP-2 and the expression of the main breast osteoblast-like cells (BOLCs) biomarkers. To further corroborate these data, an in vitro experiment for demonstrating the co-expression of nBMP-2 and RANKL or vimentin or SDF-1 in breast cancer cells that acquire the capability to produce microcalcifications was developed. These investigations confirmed the association between the nBMP-2 expression and both RANKL and SDF-1. The data supports the idea that whilst cytoplasmic BMP-2 can be involved in epithelial to mesenchymal transition phenomenon, the nuclear variant is related to the essential mechanisms for the formation of breast microcalcifications. In conclusion, from these experimental and translational perspectives, the complexity of BMP-2 signaling will require a detailed understanding of the involvement of specific BMP-2 variants in breast cancers.

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Section: Discussionmentioning

confidence: 99%

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

Scimeca

Giocondo

Montanaro

et al. 2020

Cells

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“…Our data showed a significant positive association among the sestamibi uptake and the proliferation index evaluated both in terms of the number of Ki67 positive cells and mitosis. This can be explained by (1) the capability of sestamibi to remain in the mitochondria after passive diffusion [ 14 ], (2) the increased uptake of sestamibi in mitochondria with high membrane potential [ 12 ], and (3) the role of mitochondria and their membrane potential in the cell proliferation process [ 25 ]. Of note, we also found that age affects neither the sestamibi uptake nor proliferation index in our case selection.…”

Section: Discussionmentioning

confidence: 99%

“…Irregular-shaped regions of interest (ROIs) were used to encase the lesions. The evaluation of the lesion to nonlesion ratio (L/N) was estimated according to our previous study [ 12 ]. For the patients who underwent [ 99 mTc]Sestamibi SPECT before biopsy (n = 15), the [ 99 mTc]Sestamibi SPECT-guided biopsy procedure was performed.…”

Section: Methodsmentioning

confidence: 99%

“…The parathyroid glands are able to concentrate a variety of chemical substances, including vital dyes and radiopharmaceuticals, and this ability has been exploited for localization purposes. In this scenario, over the years, numerous methods of performing parathyroid imaging with sestamibi have been suggested [ 9 , 10 , 11 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, parathyroid scintigraphy is generally used in the management of PHP patients as an imaging procedure that is capable of providing important information to schedule a minimally invasive parathyroidectomy [ 10 , 11 ]. However, recent discoveries about the ability of [ 99 mTc]Sestamibi SPECT to identify some biological characteristics of human carcinomas, i.e., breast cancers [ 12 , 13 ], can provide a scientific rationale to study the possible association between sestamibi uptake and histological characteristics of parathyroid lesions. In particular, the uptake of sestamibi in the mitochondria [ 14 ] could be related to the aggressiveness of parathyroid cancers, which histologically can appear as a high proliferation index, the presence of numerous intratumoral vessels (angiogenesis), and vascular invasion.…”

Section: Introductionmentioning

confidence: 99%

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[99mTc]Sestamibi SPECT Can Predict Proliferation Index, Angiogenesis, and Vascular Invasion in Parathyroid Patients: A Retrospective Study

Urbano

Scimeca

Russo

et al. 2020

JCM

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The aim of this study was to evaluate the possible association among sestamibi uptake and the main histopathological characteristics of parathyroid lesions related to aggressiveness such as the proliferation index (Ki67 expression and mitosis), angiogenesis (number of vessels), and vascular invasion in hyperparathyroidism patients. To this end, 26 patients affected by primary hyperparathyroidism subjected to both scintigraphy with [99mTc]Sestamibi and surgery/bioptic procedure were retrospectively enrolled. Hyperfunctioning of the parathyroid was detected in 19 patients. Our data showed a significant positive association among the sestamibi uptake and the proliferation index histologically evaluated both in terms of the number of Ki67 positive cells and mitosis. According to these data, lesions with a higher valuer of L/N (lesion to nonlesion ratio) frequently showed several vessels in tumor areas and histological evidence of vascular invasion. It is noteworthy that among patients with negative scintigraphy, 2 patients showed a neoplastic lesion after surgery (histological analysis). However, it is important to highlight that these lesions displayed very low proliferation indexes, which was evaluated in terms of number of both mitosis and Ki67-positive cells, some/rare vessels in the main lesion, and no evidence of vascular invasion. In conclusion, data obtained on patients with positive or negative scintigraphy support the hypothesis that sestamibi can be a tracer that is capable of predicting some biological characteristics of parathyroid tumors such as angiogenesis, proliferation indexes, and the invasion of surrounding tissues or vessels.

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Breast Cancer Metastasis to Bone: Look into the Future

PALUMBO

Scioli

Bonfiglio

et al. 2023

Interdisciplinary Cancer Research

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Breast-Specific Gamma Imaging with [99mTc]Tc-Sestamibi: An In Vivo Analysis for Early Identification of Breast Cancer Lesions Expressing Bone Biomarkers

Cited by 7 publications

References 33 publications

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

BMP-2 Variants in Breast Epithelial to Mesenchymal Transition and Microcalcifications Origin

[99mTc]Sestamibi SPECT Can Predict Proliferation Index, Angiogenesis, and Vascular Invasion in Parathyroid Patients: A Retrospective Study

Breast Cancer Metastasis to Bone: Look into the Future

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