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María Victoria Velázquez

Abstract Resumen

In this article, the author makes a description of the different forms En este artículo, el autor realiza una descripción de las diferentes that constitute the set of tests with molecular type images that are modalidades que constituyen el conjunto de exámenes con imáge - currently available for the study of the mammary gland. Indeed, nes de tipo moleculares que se encuentran disponibles actualmente molecular studies of the breast is becoming very useful alternative para el estudio de la glándula mamaria. En efecto, los estudios mo - for the evaluation of the primary tumor and metastatic disease. Bre - leculares de la mama se están convirtiendo en alternativas muy úti - ast Specific Scintigraphy Image (BSGI), Molecular Breast Imaging les para la evaluación de la enfermedad tumoral primaria y (MBI), Positron Emission Tomography (PET) and Positron Emis - metastásica. La Gammagrafía Específica de Mama (BSGI), las imá - sion Mammography (PEM), constitute the arsenal of studies sho - genes moleculares de la Mama (MBI), la Tomografía con Emisión wing tumor metabolic activity by uptake of a radiopharmaco. The de Positrones y la Mamografía con Emisión de Positrones (PEM), isotope is absorbed by all cells in the body and is trapped by the tumor constituyen el arsenal de estudios que revelan la actividad metabó - cells which emit gamma rays that are themselves picked up by the lica del tumor por la captación de un radiofármaco. El isótopo se gamma camera and converted into digital images. These studies are absorbe por todas las células en el cuerpo y es atrapado por las cé - more reliable in differentiating malignant cells from normal cells. lulas tumorales que emiten rayos gamma que son a su vez captados por la gamma cámara y convertidos en imágenes digitales. Estos estudios son más confiables al diferenciar células malignas de cé - lulas normales. key words: breast, molecular, PET. Palabras claves: mama, molecular, PET.

Introduction rate for patients. Xeromammography, analog mammography, digi - Anatomy images are the basis for the detection of tal mammography and ultrasound detect cancer breast cancer since the implementation of the mam - characterizing the morphological appearance of tu - mography in the 70s and ultrasound in the 80s. mors. This requires for analysis patterns on the ap - Prior to that, breast cancer could only be detected pearance of the tumor, whether it is a mass, an when it was clinically evident, as a palpable mass. architectural distortion or a calcification. At that time, breast imaging was opening new When cancer is visible in mammography or ul - doors, which made the detection of breast tumors trasound the tumor growth has already exceeded possible since they were identified in a two-dimen - one trillion of cells in a process, which lasts more sional plane and, thus, there was a better survival than 10 years.

Datos de contacto: María Victoria Velásquez, M.D. Lynn Cancer Institute. Boca Raton Regional Hospital. Recibido:  de diciembre de  / Aceptado:  de febrero de   Meadows Road Boca Raton, Florida  - U.S.A Recieved: December th  / Accepted: February st  e-mail: [email protected]

Vol.  / Nº - Abril, .  Molecular imaging in the evaluation of the breast Velázquez, M. V.

More recently, the use of Magnetic Resonance vessels to form, that moment is when more cell re - (MR) has increased in the evaluation of the breast. plication takes place. Our goal as breast radiolo - This functional imaging method detects breast tu - gists must be the detection of cancer before mors due to their neovascularization. When tumors neovascularization starts. develop, there is initially a diffusion of nutrients and oxygen from the interstitial tissue. In a given time, cells become hypoxic since that diffusion is insuf - Types of molecular breast imaging ficient to maintain the growth. That is when che - motactic agents are released as Vascular Endothelial Molecular breast studies are becoming very useful Growth Factor (VEGF), which can cause the forma - alternatives for the evaluation of the primary and tion of new abnormal blood vessels around the metastatic tumor disease. tumor. These vessels have a discontinuous base - Breast-Specific Gamma Imaging (BSGI), Molecular ment membrane causing an escape from fluids Breast Imaging (MBI), Positron Emission Tomo - around the tumor. graphy (PET) and Positron Emission Mammography The dynamic study with a contrast agent in MR (PEM) constitute the repertoire of studies, which re - evaluates the process of neovascularization to arrive veal the metabolic activity of the tumor through a at the diagnosis of cancer. When looking at the radiopharmaceutical uptake. three-dimensional signal before and after the con - The isotope is absorbed by the cells in the body trast injection, the change in the time of that enhan - and trapped by tumor cells emitting gamma rays, cement is evaluated and this permits an estimate of which at the same time, are detected by the gamma the probability of malignancy. This is how a two- camera and turned into digital imaging. These stu - dimensional level becomes four-dimensional since dies are more reliable since they differentiate ma - a fourth dimension is added to the three-dimensio - lign from normal cells. nal image, i.e., time. The goal for the 21st century is to identify breast cancer before they are palpable or evident with the Scintimammography conventional anatomy detection tools. Molecular breast imaging is available since 1990 This is a nuclear study used to evaluate tumor cells through the evaluation with the Positron Emission based on their metabolism. The use of Technetium Tomography (whole body PET). This technique is 99 (Tc99) Sestamibi for the detection of breast can - excellent for the identification of metastatic lesions cer was reported in 1992 during its evaluation as a related to breast cancer; however, it is limited for cardiac agent. Since then multiple techniques have the identification and location of small tumors in been evaluated using planar computed tomography the mammary gland. Any type of study, which de - with single photon radioisotope emission and con - tects the metabolic activity of the individual cells, ventional gamma cameras for the detection of bre - has the potential of making the distinction between ast cancer (1). Tailefer reported in a meta-analysis normal and abnormal cells. This is the essential with 5,660 patients a sensitivity of 84% and a spe - process of the images with PET. cificity of 86% (2). However, in tumors with a size Cancer is known to have an uncontrolled cell re - of less than 15 mm, the sensitivity was as low as plication developing an increased metabolism of 50%. the glucose. Its distribution among normal and ab - Conventional gamma cameras are not widely normal cells is evaluated through a radioactive glu - used in breast imaging due to the 18% of resolution cose injection (F18 FDG). energy and the excessive distance between the Understanding the identification mechanism of organ and the detector, which does not permit the tumor cells with PET and MR, it seems like PET has detection of small tumors. In order to make up for the ability to detect cancer in an earlier stage than this and taking into account the potential that the MR does. The increase in the production of energy scintimammography offers in breast evaluation, in the cell occurs before there is incitement for new specific cameras have been developed for the eva -

 Revista Argentina de Diagnóstico por Imágenes Molecular imaging in the evaluation of the breast Velázquez, M. V.

luation of the gland. Bsgi: breast-specific gamma imaging The new cameras have a resolution of 3 mm and they obtain images similar to the mammography. As mentioned before, photons emission is detected The distance between the camera and the object by the new special camera for the breast. These was reduced with this new configuration, only vi - cameras have a head of compact detectors in a sualizing the breast. This new cameras permitted space of 6 x 8 x 4 inches. Each detector has 3000 and increase of 85% in the sensitivity of the study crystals of Sodium Iodide and 48 multiplying tubes, in lesions smaller than 1 cm (3). which are sensitive to the position. The detectors are easy to handle and they have direct contact with the breast and the thoracic wall, minimizing the Grounds for breast imaging with dead space (Figure 1). technetium 99m Sestamibi This configuration with a head of detectors and a compression plate allows for the detection of le - Scintimammography purely offers physiological sions as small as 3 millimeters and they resemble information due to the cell uptake of the radioactive standard mammography projections. The camera tracer (Sestamibi), which is retained in the tumor is small and portable eliminating modifications in cells due to its abnormal metabolism. The emitted installation and workspace (6). radiation in photons from these cells is detected with a specific gamma camera converting that sig - nal into functional images or hot spots (4). The iso - tope used is Technetium 99 Sestamibi, a lipophilic agent, which accumulates in the mitochondrion. The 99 Tc lasts for 6 hours and produces 140 KeV photons. The affinity of the breast tumor cells though the ra - diopharmaceutical has two mechanisms: 1 - The agent is distributed regularly through the circulatory system but it accumulates in malign tu - Fig. : Detection of photons, which are emit - mors due to their neovascularization. ted from the breast and uptook by de - 2 - Tumor cells have a greater mitochondrial cyto - tectors located in the camera. plasmic density and also, there is a greater electric potential in its membrane, allowing the radiophar - maceutical to be retained in the mitochondrion. These two mechanisms make the scintimammo - graphy a very specific and sensitive study (5). Bsgi technique Currently, there are two techniques of breast ima - ging using this imaging principle: The patient gets an intravenous injection of 25-30 BSGI: Breast-Specific Gamma Imaging mCI (1110 mBq) of Tc 99 Sestamibi in the antecu - MBI: Molecular Breast Imaging bital vein (ideally on the arm opposed to the area of the detected cancer to avoid ambiguities due to The difference between these two techniques is the increase of the uptake in the armpit). based on the quantity of administered isotope and Ten minutes after the injection, the images are in - the type of gamma camera used to obtain the image itiated with the patient seated in the camera, using as described below. craniocaudal and mediolateral oblique projections (Figure 2).

Vol.  / Nº - Abril, .  Molecular imaging in the evaluation of the breast Velázquez, M. V.

Fig. : a-b Equipment used for the record of photons similar to the conven - tional mastography with a slate of detec - tors and a slate of compression.

Bsgi results In another series, the efficiency of BSGI was de - monstrated when identifying hidden tumors, which Dr. Rachel Brem and her collaborators have perfor - were not seen with mammography and it determi - med several important clinical studies using BSGI. ned the real extension of the disease, helping to These series represent early experiences with a optimize the surgical handling. This technique de - technology, which still has not gained popularity in monstrated a sensitivity of 91% for the evaluation the United States. of DCIS compared to the MRI that has a sensitivity In one of the series, BSGI was evaluated as a se - of 73%. The study helped arrive at the conclusion cond modality for the assessment of breast cancer. that BSGI demonstrated DCIS better than MRI or BSGI detected 80 of the 83 malign lesions assessed mammography (8). with a sensitivity of 96% and correctly identified 50 In a recent study, the same group of investigators of the 84 benign lesions as negative with a specifi - compared the usefulness of BSGI and MRI in city of 60%. In this series, invasive tumors and sma - women with inconclusive mammographies. The llest tumors in Situ had a size of 5 mm. The study demonstrates that BSGI has a similar sensitivity technique visualized cancer, which were not detected to MRI but shows a greater specificity. (Table 1). with mammography or ultrasound in 6 patients (7).

Sensitivviity SpVecificity PP NPV

MRI

TaTba. bla. 1

False negatives as low as 6.3% have been demons - trated in this study (9). The study concludes that there are other series required with more patients suffering from breast cancer. The disadvantages of this technique include the glandular radiation doses of 8 – 9 mSv and the fact that it is not widely available for the diagnosis or interventionism directed with BSGI.

 Revista Argentina de Diagnóstico por Imágenes Molecular imaging in the evaluation of the breast Velázquez, M. V.

MBI: molecular breast imaging

It is a modification of BSGI. It uses the same ra - dioisotope in a smaller quantity: 4 – 8 mCi and an improved gamma camera in equipment similar to mammography. This new configuration has two groups of detectors that are located in each of the compression plates and in direct contact with the breast when the image is obtained (Figure 3). The detectors of this unit use Cadmiun Zinc Tellu - ride (CZT), that is to say, they do not have crystals or photomultipliers like BSGI camera gamma. This permits resolution energy of 3-4%. In other words, the intrinsic resolution now depends on the detec - tor. Diffuse radiation is avoided and contrast is im - proved because the gamma energy is directly converted into signal. It has pixels of 1.6 x 1.6 mm and a field of image of 20 x 24 cm. Another very important element in this new de - sign is the registered collimation. These collimators are, perhaps, the most important component of ca - mera gamma since they improve the spatial resolu - tion and the sensitivity of the photons. This configuration permits the detection of le - sions smaller than 10 mm. Fig. : New equipment designed as conven - tional mammography equipment with two slates of detectors. MBI technique

The patient gets an intravenous injection of 4-8 mCI The description of the findings with BSGI or MIB must (355 mBq) of Tc 99 Sestamibi in the antecubital vein be adjusted to the ACR lexicon for Magnetic Reso - (ideally on the arm opposed to the area of the de - nance. First, the general uptake of the tissue will be tected cancer to avoid ambiguities due to the incre - described and then the morphology of the uptake ase of the uptake in the armpit). focal point, whether it is a mass or not, with its corres - Five minutes after the isotope injection, the ac - ponding measures and precise location. The relevant quisition of 4 mammographic standard projections BIRADS category must be equally assigned. with slight compression is initiates, in a period of 40 minutes in total. One of the greatest advantages of this new tech - nique is that the effective dose of glandular radia - tion with de Tc99m sestamibi 4-8 mCi is of 1.5 -3.0 mSv, very close to the conventional mammography, which is of 0.7-1.0 mSv. The obtained images are interpreted basing on the detection of uptake focal points. Mammogra - Fig. : Images obtained in the MBI equipment, phies must be correlated with other available breast showing the four superior conventional studies (Figure 4). images and four inferior images. These are bidimensional images.

Vol.  / Nº - Abril, .  Molecular imaging in the evaluation of the breast Velázquez, M. V.

Indication tients in the last years show that MBI has a poten - tially important role as a complement of mammo - -- Dense breast tissue. BSGI and MBI are not af - graphy in the diagnosis and screening scenarios. fected due to the glandular density as happens with mammographies and MRIs. - Staging in patients with a recent diagnosis of bre - Disadvantages of BSGI and MBI ast cancer or when there is a suspicion of multiple lesions or groups of micro-calcifications to deter - - There are not enough clinical studies showing the mine the extension of the primary tumor and assess usefulness of this techniques compared to MRI and treatment options. Mammography. - Assessment of palpable lesions not detected with - The acquisition of images takes a long time. mammography or ultrasound. - Glandular radiation doses greater than in mam - - Post-surgical patient with positive tumor margins. mographies, especially with BSGI. The scar tissue is not a limiting factor for the eva - - Equipment for images and biopsies are not widely luation with BSGI or MBI. available. - Patients in hormones replacement therapy. - The resolution of these techniques is bidimensio - - Detection of hidden primary tumor. nal, i. e. planar. - Assessment of the axillary ganglion state. - The uptake cannot be quantified as in PEM. - Assessment of high risk patients with a history in the family, with BRCA 1 or BRCA 2 gene mutations MIB has demonstrated in several clinical studies a with a history of non-typical lesions or diagnosis sensitivity of 93/95% and a specificity of 79/85%, prior to breast cancer. being a technique that can be used as a comple - - Inconclusive mammography or ultrasound results. ment of other breast imaging modalities for the eva - luation of problematic or undetermined cases (10). Advantages of BSGI and MBI Positron emission tomography (PET) When MRI and BSGI/MBI are compared, several factors that should be taken into account: The principles of PET and PEM images are based - These techniques use fewer images while MRI on the use of 2-deoxy-2-(18F) Fluoro-D-Glucose, uses hundreds of them. known as FDG, an analog positron emission of glu - - The projections are similar to the mammography cose that detects metabolic alterations inside tumor with fast and easy interpretation. - The learning cells. This mechanism works because the malign curve is easier for radiologists. cells need more glucose and secrete more GLUT-1 - BSGI and MBI are obtained with a more comfor - (glucose transporter). FDG is rapidly absorbed, it table position for the patient without compression. is not metabolized and it is retained inside the ma - - Claustrophobia or renal problems are not limiting lign cells. This accumulation of the radioisotope is factors. uptook by the camera and converted into an image. - They cost 37% less than MRIs and twice the price FDG has a mean life of 110 minutes, it produces of a mammography. a 511 KeV photon and it is expelled through posi - - They are not affected by the tissue density, the tron emission. An electron destroys a positron du - menstruation period or the use of hormones repla - ring this process, creating 2 gamma rays that are cement. emitted in opposite directions and are uptook by - They offer a high degree of assurance when a re - detectors located in opposing extremes of the ca - sult is negative. This plays a very important role in mera to be later converted into a digital signal to the handling of BIRADS 3 or 4, avoiding unneces - create the image. Lesions can be exactly located sary biopsies and control studies. with this configuration (Figure 5). - Studies performed in Clínica Mayo in 1500 pa - PET has shown to be very sensitive and effective

 Revista Argentina de Diagnóstico por Imágenes Molecular imaging in the evaluation of the breast Velázquez, M. V.

for the detection of advanced cancer and distant metastases (Figure 6). In the whole-body PET scan, detectors are loca - ted far away from the objective, which creates an attenuation of gamma rays, decreased spatial reso - lution and insufficient counting of photons accu - mulation. Several studies show that the detection rate with whole-body PET has a range of sensitivity of 80/100% and a range of specificity of 75/100% with an accurate diagnosis in 70/97% of cases. However, the high sensitivity was only reported in large tu - mors (11). Fig. : Emission of rays created by the destruction of positrons and uptook by detectors located in op - Positron emission mammography posing sides of the camera (PEM)

PEM uses the same image principles as PET with similar projections to the mammography. It is a high-resolution study, specialized in breast molecu - lar images. In 1993, Thompson introduced this technology with 2 plane detectors located on both sides and compressing the breast. He found a high effective - ness in the counting of photons accumulations due to the proximity of the detectors to the gland. This resulted in a better space resolution compared to whole-body PET (12-13). The first images were ob - tained in a stereotaxic table assembled by the de - tectors. The system permitted a good radiography correlation with the mammography; however, the little visualization of posterior breast tissues was a limiting factor. The second scanner was portable, similar to a small mammography unit with a computerized sta - tion for the acquisition of images. The 2 detectors contain 2000 photo detection crystals located inside the compression slab. These detectors are moved while there is an uptake of the counting emitted from the gland (14). Detectors emit a tridimensio - nal digital signal.

Fig. : Whole-body PET showing an abnormal a uptake of the FDG by the invasive ductal b carcinoma and by left axillary adenopathy

Vol.  / Nº - Abril, .  Molecular imaging in the evaluation of the breast Velázquez, M. V.

Imaging principles with PEM inside tumor cells. PEM is designed to visualize and measure this accumulation. As mentioned before, tumor cells have certain ab - PET and PEM use the same imaging principles; normal biological characteristics, such as glucose however, the camera used in PEM has been modi - metabolism, cell overgrowth, hypoxia, and perfu - fied to detect small breast tumors (Figure 7). sion patterns. Taking advantage of these metabolic irregularities, FDG is used to assess its accumulation

Fig. : a b Phantom showing PEM resolution (A) compared to PET resolution (B).

D ifferences in the configuration of P ET and PEM

PEM indications preventive therapy. - Inconclusive studies like mammography or ultra - - Identification of the tumor extension in patients sound. with a recent diagnosis of breast cancer. - Screening of high risk patients, with a history of - Patients with primary unknown tumor. breast cancer or gene mutations. - Assessment in the recurrence of breast cancer. - Monitoring the response in chemotherapy pa - - Follow-up of patients with high-risk lesions or in tients.

 Revista Argentina de Diagnóstico por Imágenes Molecular imaging in the evaluation of the breast Velázquez, M. V.

- Patients with MRI as a contraindication so they re - To quantify the counting, the standardized uptake quire a functional study. value is used in PET, known as SUV. In PEM, PUV Diabetic patients are not candidates for PEM since or PEM uptake value are used, since it is performed high levels of glucose dissolve the radioisotope and with a limited scanning angle and it does not have high levels of insulin cause FDG to be accumulated corrected attenuation. in the muscle tissue. A radiologists specialized in breast imaging must be the one who interprets the study. First, the study should be described and the glandular tissue up - Technique take should be quantified. An increase in the glan - dular uptake results in an increase of the PUV. Berg Patients must have a strict diet high in proteins and reported that the maximum PUV is 0.33 in the adi - low in carbohydrates the day before. They must pose tissue, 0.41 in the dispersed tissue, 0.65 in the fast for 4 hours prior to the exam. The exam is con - heterogeneous tissue and 0.85 in the dense tissue traindicated if the level of glucose is greater than (15). 140 mg/dl in the moment of the exam. Traditionally, Then, the uptake areas or hot spots are described. F18FDG 10 mCI are injected; however, it has been The description should include the morphology, proved that 5 and even 3 mCI are equally useful, size, location and quantification with PUVmax. An decreasing radiation and costs. After the injection, additional value is generated called LTB (Lesion to the patient must rest for one hour. During that Background ratio), which is the ratio between the time, some control measures are taken: PUV quality lesion PUVmax and the tissue PUVmean. and reproducibility at the image acquisition stage. The first image obtained shows the location of the injection to guarantee there is no drug extrava - LTB= lesion PUV max sation. With the patient in a sitting position, the bre - Tissue PUV mean ast is immobilized with a slight compression; then craniocaudal and mediolateral oblique projections According to Berg, who discovered LTB, it increases of each breast are obtained. It is important to make with the nuclear degree of the lesion. That is how sure that the entire breast is included in the image the LTB of atypical ductal hyperplasia is approxi - field, especially the armpit. Each projection is ob - mately 1.45, the DCIS is 2.1 and the invasive carci - tained in a period of 10 minutes, counting emitted noma is 3.4 or more. Lobular carcinomas showed photons in a complete way. If it is necessary, some an LTB of 1.49 (16). This is important when consi - additional projections can be made, like in the dering that PEM can be useful in the evaluation of mammography, to try to include the entire tissue. high-risk patients where MRI has a limited specifi - The study must be performed by a technologist city. It should also be considered when valuing the with knowledge of mammography who previously response to chemotherapy in triple-negative breast has to examine the breast images available to de - cancer cases as described by Wei Tse in a study pu - termine special projections. blished in RSNA in 2011. It should be pointed out that the dose of glandu - PEM is able to detect Atypical Ductal Hyperplasia lar radiation with an injection of 10 mCI is 7 mSV (ADH) and can be used to monitor prophylactic and 5 mCI is 3.5 mSV, and that the resolution in the therapies (Figure 8). images is not affected with a reduction of the dose. Using reconstruction techniques with limited angle, 12 tomographic images are compiled in each of the projections obtained. Images are examined in a computerized workstation to assess the mea - sures, distances, areas of interest and values of stan - dard uptake, known as PUV.

Vol.  / Nº - Abril, .  Molecular imaging in the evaluation of the breast Velázquez, M. V.

Fig. : a b PEM showing right invasive carcinoma (A) and left HDA (B) (Arrows).

When interpreting the study, the history of the pa - 92% compared with the sensitivity of PET of 39%. tient and available breast studies must be correla - PEM and MRI sensitivity was similar. PEM identified ted. PEM reports must keep to BIRADS descriptors 93% of DCIS. PEM has half of the false positives that in spite of not being published by ACR yet, compared to MRI, resulting in a specificity of 73% they are adapted to the ones recommended for for PEM and 43% for MRI. These findings were MRI. consistent, regardless of glandular density. The If lesions not identified with mammography are conclusion of this study is that perhaps PEM is identified with PEM, targeted ultrasound is used to more useful in the screening of high-risk patients characterized those lesions and perform an ultra - due to gene mutations, avoiding unnecessary biop - sound biopsy in them. PEM guided biopsies have sies and identifying cancer in its early stages (19). been performed successfully in the US and have In a multicenter study published by Berg, PEM been approved by the Food and Drug Administra - and MRI are confirmed to have a similar sensitivity. tion (FDA) since 2008. In this study, PEM specificity was also greater than It should be taken into account that when there MRI, the predictive positive value for biopsy by is lesion uptake by PEM, it should be handled im - PEM was 63% and for MRI it was 53%. The study mediately since there is no possibility of BIRADS 3 concludes that the combination of the anatomic and category in PEM. (17) metabolic characterization of lesions improves the detection of an additional disease from a 49 to a 60% (20). PEM results

The first pilot study with PEM was performed with Conclusion a first-generation scanner by Tafra and collabora - tors. This study examined patients in conservative Even though mammography continues to be the surgical therapy. PEM correctly predicted 73% of gold standard in breast cancer screening, other patients with positive surgical margins and 100% of techniques are emerging that are providing infor - patients with negative margins. mation beyond the morphological state of the le - The study concludes that PEM has a high value sion, revealing fascinating information about in surgical planning (18) molecular aspects of the cancer. This opens a new In a multi-institutional study, the performance of spectrum of options for patients. PEM was evaluated in patients with known cancers The current tendency in images and treatment of or suspicious lesions. PEM showed a sensitivity of breast cancer is individualization. Personalized tre - 91%, a specificity of 93%, a VNP of 88% and a diag - atment is becoming more common based on the nosis accuracy of 92%. PEM made a preparatory biological and biomolecular characteristics of the diagnosis of 91% of DCIS (15). tumor, as well as the presence of predictive mole - Schilling compared the usefulness of PET, PEM y cular indicators. In the same way, breast images MRI demonstrating that PEM has a sensitivity of are in search of tumor indicators such as cell over -

 Revista Argentina de Diagnóstico por Imágenes Molecular imaging in the evaluation of the breast Velázquez, M. V.

growth or estradiol analogue that can be matched 18:111-117 to radioisotopes and be used to monitor and pre - 11. Rose C. Positron emission tomography for the dict the clinical response to individualized or hor - diagnosis of breast Cancer. Nucl Med Comm. 2002: mone techniques. PET, PET and BSGI/MBI are 23; 623-618. techniques with a high potential to be used in this 12. Thompson CJ, Murthy K, Picard Y, Weinberg IN, field; however, more research is needed with a gre - Mako, R. Positron Emission Mammography (PEM) ater number of patients to demonstrate its real im - A Promising Technique for Detecting Breast Cancer. pact. IEEE Trans. Nucl. Science 142: 1012- 1017 (1995). 13. Thompson CJ, Murthy K, Weinberg IN, et al. Fe - asibility Study for Positron Emission Mammography. Referencias Med Phys 21: 529-538 (1994). 14. Thompson CJ, Murthy K, Picard Y, Wang B, 1. Beyhan AC. Clinical experience with Tc 99m Clancy R,Weinberg IN. Imaging Performance of MIBI imaging in patients with malignant tumors; PEM: A Metabolic Imaging System for the Early De - preliminary results and comparison with TI-201. tection of Breast Cancer. Radiology 1995: 1975; 319. Clin Nucl Med 1992; 17:171-176. 15. Weinberg IN, Beylin D, Anashkin E, et al. Ap - 2. Tailefer B. Clinical applications of 99m Tc-sesta - plication of a PET Device with 1.5mm FWHM In - mibi scintimammography. Semin Nucl Med 2005; trinsic Spatial Resolution to Breast Cancer Imaging. 35: 100-115. Proceedings of the 2004 IEEE International Sympo - 3. Brem RF. High resolution scintimammography: sium on Biomedical Imaging: From Nano to Macro, a pilot study. J Nucl Med 2002; 43: 909-915. Arlington ,VA, USA. 15-18 April, 2004: p1396-1399 4. Brem RF. Occult breast cancer scintimammo - (2004). graphy with high resolution breast specific gamma 16. Berg WA, Weinberg IN, et al. High Resolution camera in women at high risk for breast cancer. Ra - Fluorodeowyglucose Positron Emission Tomo - diology 2005; 237: 274-280. graphy with Compression is Highly Accurate in De - 5. Minhao Z. Real-world application of breast-spe - picting Primary Breast Cancer. The Breast Journal, cific gamma imaging, initial experience at a com - Vol12, November 4, 2006, 309-323. munity breast center and its potential impact on 17. Narayan, D, Interpretation of PEM and MRI by clinical care. Am Journ of Surg 2008; 195: 631-635. experienced breast imaging radiologist: Perfor - 6. O’Connor MK. Molecular breast imaging: ad - mance and Observer reproducibility. AJR 2011: 196: vantages and limitations of a scintimammographic 971-981. technique in patients with small breast tumors. Bre - 18. Tafra L, Cheng Z, Uddo J, et al. Pilot Clinical ast J 2007; 13: 3-11. Trial of 18F- fluorodeoxyglucose Positron Emission 7. Brem RF. Breast-specific gamma imaging as an Mammography in the Surgical Management of Bre - Adjunct imaging modality for the diagnosis of breast ast Cancer. Am J Surg. 2005: 190: 628- 632. cancer. Radiology 2008; 247: 651-657. 19. Schilling K, Narayanan D, Kalinyak J. Effect of 8. Brem Rf. Detection of Ductal Carcinoma in Situ Breast Density, Menopausal Status and Hormone with mammography, Breast-specific gamma ima - Use in High Resolution Positron Emission Mammo - ging and Magnetic resonance imaging: A compara - graphy. Abstract RSNA, 2008, Chicago, IL, USA. tive study. Acad Radiology 2007; 14: 8. 20. Berg WA. Comparative effectiveness of PEM 9. Brem RF. Breast-specific gamma imaging with and MRI for presurgical planning of the ipsilateral 99m Tc-Sestamibi and Magnetic Resonance Imaging breast in women with breast cancer. Radiology in the diagnosis of Breast Cancer-A comparative 2011, 258: 59-72. Study. Breast J 2007; 13: 465-469. 10. Siegal E. Breast Molecular Imaging: A retros - pective review of One institution's experience with this modality and analysis of its potential role in breast imaging decision making. Breast J 2012;

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