18F-Alfatide II for the evaluation of axillary lymph nodes in breast cancer patients: comparison with 18F-FDG

doi:10.21203/rs.3.rs-166779/v1

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18F-Alfatide II for the evaluation of axillary lymph nodes in breast cancer patients: comparison with 18F-FDG

https://doi.org/10.21203/rs.3.rs-166779/v1

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published 09 Feb, 2022

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¹⁸F-Alfatide II has been translated into clinical use and been proven to have good performance in identifying breast cancer. In this study, we investigated ¹⁸F-Alfatide II for evaluation of axillary lymph nodes (ALN) in breast cancer patients and compared the performances with ¹⁸F-FDG.

Methods: A total of 44 female patients with clinically suspected breast cancer were enrolled and underwent ¹⁸F-Alfatide II and ¹⁸F-FDG PET/CT within a week. Tracer uptakes in ALN were evaluated by visual analysis, semiquantitative analysis with maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean) and SUV_max ratio of target/non-target (T/NT).

Results: Among 44 patients, 37 patients were pathologically diagnosed with breast cancer with metastatic (17 cases) or non-metastatic (20 cases) ALN. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of visual analysis were 70.59%, 90.00%, 81.08%, 85.71% and 78.26% for ¹⁸F-Alfatide II, 64.71%, 90.00%, 78.38%, 84.62% and 75.00% for ¹⁸F-FDG, respectively. By combining ¹⁸F-Alfatide II and ¹⁸F-FDG, the sensitivity significantly increased to 82.35%, the specificity was 85.00%, the accuracy increased to 83.78%, the PPV was 82.35% and the NPV significantly increased to 85.00%. Three cases of luminal B subtype were false negative for both ¹⁸F-Alfatide II and ¹⁸F-FDG. The other 2 false negative cases of ¹⁸F-Alfatide II were triple-negative subtype and 3 false negative cases of ¹⁸F-FDG were luminal B subtype too. The AUCs of three semi-quantitative parameters (SUV_max, SUV_mean, T/NT) for ¹⁸F-Alfatide II were between 0.8 and 0.9, whereas those for ¹⁸F-FDG were more than 0.9. ¹⁸F-Alfatide II T/NT had the highest Youden index (76.5%), specificity (100%), accuracy (89.19%) and PPV (100%) among these semi-quantitative parameters. ¹⁸F-Alfatide II uptake as well as ¹⁸F-FDG uptake in metastatic axillary lymph nodes (MALN) was significantly higher than that in benign axillary lymph nodes (BALN). Both ¹⁸F-Alfatide II and ¹⁸F-FDG did not show difference in primary tumor uptake irrespective of ALN status.

Conclusion: ¹⁸F-Alfatide II can be used in breast cancer patients to detect metastatic ALN, however, like ¹⁸F-FDG, with high specificity but relatively low sensitivity. The combination of ¹⁸F-Alfatide II and ¹⁸F-FDG can significantly improve sensitivity and NPV. ¹⁸F-Alfatide II T/NT may serve as the most important semi-quantitative parameter to evaluate ALN.

Nuclear Medicine & Medical Imaging

18F-Alfatide II

integrin αvβ3

positron emission tomography

breast cancer

axillary lymph node

Axillary lymph nodes (ALN) are the most common spread site of breast cancer (1, 2). The status of ALN determines the staging, treatment strategy and prognosis for breast cancer patients (3). ALN involvement often means the more advanced stage, the greater extent of surgery, the need for systemic therapy and the lower survival rate. ALN metastasis is also the most important predictor of overall recurrence and survival (4). Therefore, the identification of ALN metastasis is crucial for patients with breast cancer. The gold standard for detecting ALN involvement is ALN dissection, which however can bring many adverse complications such as arm edema, pain, neuropathy, and so on (5). Although minimally invasive methods including sentinel lymph node biopsy, core needle biopsy and fine needle aspiration cytology lead to fewer complications than ALN dissection, they have the risk of implantation metastasis (6). For these reasons, a non-invasive method of evaluating ALN is essential.

X-ray mammography, ultrasound, CT and magnetic resonance imaging (MRI) are traditional imaging methods, which can non-invasively evaluate ALN. However, the evaluation using these imaging methods is based on anatomical abnormalities and morphological changes, which often fail to reflect the status of ALN accurately (1). As a molecular imaging method, positron emission tomography (PET) has its superiority to traditional imaging methods in the clinic. It has been widely accepted for the diagnosis, staging, treatment evaluation and recurrence monitoring in cancer patients. As the most frequently used PET tracer, ¹⁸F-FDG can provide glucose metabolism information in tissues. Many ¹⁸F-FDG PET or PET/CT studies have also shown promising results for ALN evaluation. It has been reported that the specificity of ¹⁸F-FDG for detecting metastatic ALN is up to 90–100%, but the sensitivity is relatively low to 50–80% (7–9). Accordingly, ¹⁸F-FDG PET or PET/CT may underestimate the number of metastatic ALN. Therefore, more accurate ALN assessment entails some emerging PET tracers.

¹⁸F-Alfatide II is an arginine-glycine-aspartate (RGD) based PET tracer targeting integrin α_vβ₃, which is highly expressed on activated endothelial cells of tumor neovasculature (10, 11). Some studies have shown the usefulness of ¹⁸F-Alfatide II for tumor detection, therapy response prediction and prognosis evaluation (12–20). One of our previous clinical studies also demonstrated that ¹⁸F-Alfatide II has good performance in identifying breast cancer. Particularly, ¹⁸F-Alfatide II may be superior to ¹⁸F-FDG in detecting breast cancer with strongly positive ER but negative HER-2 expression (21). Moreover, another clinical study also indicated that this tracer is valuable in the diagnosis of metastatic lymph nodes for non-small cell lung cancer patients (22). However, there is yet no report concerning ¹⁸F-Alfatide II in detecting metastatic ALN of breast cancer.

In this work, ¹⁸F-Alfatide II was further investigated in breast cancer patients for assessing ALN on the basis of our previous study (21). We obtained diagnostic parameters of ¹⁸F-Alfatide II for identifying ALN metastasis using visual and semi-quantitative methods and assessed its diagnostic performance as compared to ¹⁸F-FDG. We also compared diagnostic parameters of ¹⁸F-Alfatide II and ¹⁸F-FDG among different groups of ALN.

Patients

This study was approved by the ethics committee of Jinling Hospital (Approval No. 2015NZYW-007) and registered at ClinicalTrials.gov (NCT02582801). The including criteria include: (1) clinically suspected primary breast cancer according to conventional imaging, (2) no prior treatment for breast lesions, (3) 18 y < age < 70 y. The excluding criteria include: (1) pregnancy or lactation period, (2) some accompanied serious diseases (e.g., impaired liver or renal function, active tuberculosis, another malignant tumor). Forty-four female patients (age range, 28–66 y, mean age, 50.73 ± 8.01 y) were included in this study and written informed consent was obtained from each patient.

PET/CT Acquisition

¹⁸F-Alfatide II was synthesized according to the previously described method (23). PET/CT scans with ¹⁸F-Alfatide II and ¹⁸F-FDG were performed with an interval of at least one day and completed within one week. No specific patient preparation was requested before ¹⁸F-Alfatide II injection, but fasting for at least 6 h was requested before ¹⁸F-FDG injection. The injected activity was 306 ± 80 MBq (range 155–503 MBq) for ¹⁸F-Alfatide II and approximately 3.7 MBq/kg body weight for ¹⁸F-FDG. In addition, blood glucose level below 140 mg/dL needs to be confirmed before ¹⁸F-FDG injection. After a rest for 60 min after injection, patients underwent the scans using an integrated PET/CT system (Biography 16, Siemens Healthcare). CT acquisition was initially performed with 120 kV, 140 mA, and a slice thickness of 5 mm. Subsequently, PET acquisition was performed with 3 min for each bed position. The CT data were used for PET attenuation correction and PET images were reconstructed using an iterative algorithm.

Image Analysis

PET, CT, and fused images were displayed on a Siemens/Syngo user interface. The images were interpreted by a consensus of two experienced nuclear medicine physicians, who were blinded to the histological diagnosis and other imaging results. It was defined as visually positive that the radioactive uptake of the ALN was higher than that of the surrounding normal tissue. The maximum standardized uptake value (SUV_max) and the mean standardized uptake value (SUV_mean) were semi-quantitatively measured by drawing regions of interest over the ALN. The SUV_max ratio of the ALN on the same side of the breast lesion to the node on the opposite side was calculated as T/NT (target/non-target).

Statistical Analysis

Statistical analysis was performed using SPSS software (version 17.0, SPSS, Inc., Chicago, IL, USA). All semi-quantitative data were expressed as the mean ± standard deviation. Differences both in independent samples and in paired samples were analyzed by t-test. The sensitivity, specificity, accuracy, PPV and NPV were calculated for each diagnostic parameter. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. The area under the curve (AUC) and the cutoff value were further determined at the point with the highest Youden index. A P value less than 0.05 was considered statistically significant.

Pathological Findings

All 44 patients received biopsy or surgery on breast lesion after two PET/CT scans. Among them, 39 patients were pathologically diagnosed with breast cancer and the other 5 were diagnosed with benign breast disease. In 39 patients with breast cancer, 2 patients did not undergo biopsy or surgery on ALN thus unclear about the metastasis status. The pathological results of ALN were obtained in the remaining 37 breast cancer patients, out of which 17 cases were confirmed with ALN metastasis and 20 cases were without. Characteristics of these 37 patients are presented in Table 1. Based on immunohistochemistry and fluorescence in situ hybridization (FISH), the invasive carcinomas in 33 patients (excluding 4 patients with ductal carcinoma in situ) were further divided into four molecular subtypes. ALN metastasis occurred in 2 cases of luminal A subtype (2/5), 8 cases of luminal B subtype (8/14), 3 cases of HER-2 overexpressing subtype (3/4) and 4 cases of triple-negative subtype (4/10).

Table 1
Characteristics of Breast Cancer Patients for Assessing ALN
Variable Breast Cancer (n)
Median Age (years, range) 53 (28–66) Histology 37 Ductal Carcinoma in situ 4 Invasive Carcinoma 33 Molecular Subtype 33 Luminal A 5 Luminal B 14 HER-2 overexpressing 4 Triple-negative 10 Axillary Lymph Node 37 Metastasis 17 No Metastasis 20

Visual Assessment Findings

Among 17 cases with ALN metastasis, 12 cases were correctly recognized using ¹⁸F-Alfatide II (Fig. 1) and 5 cases were false negative (Fig. 2). In comparison, 11 cases were correctly identified using ¹⁸F-FDG (Fig. 1) and 6 cases were false negative (Fig. 2). By combining ¹⁸F-Alfatide II and ¹⁸F-FDG, the number of false negative cases was three. Among 20 cases without ALN metastasis, 18 cases were true negative, and 2 cases were false positive using ¹⁸F-Alfatide II. Likewise, the number of true negative cases was 18 and that of false positive cases was 2 for ¹⁸F-FDG. There was one false positive case for both ¹⁸F-Alfatide II and ¹⁸F-FDG. By combining the two tracers, the number of false positive cases was three. The corresponding sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) are shown in Table 2. Both ¹⁸F-Alfatide II and ¹⁸F-FDG had the same high specificity (90.00%) and relatively low sensitivity (70.59% vs. 64.71%). They both had similar accuracy (81.08% vs. 78.38%), PPV (85.71% vs. 84.62%) and NPV (78.26% vs. 75.00%). Moreover, the combined sensitivity and NPV significantly increased to 82.35% and 85.00%, while the combined accuracy increased to 83.78%.

Table 2
Visual Analysis of ¹⁸F-Alfatide II and ¹⁸F-FDG in Identifying ALN Metastasis
Variable Sensitivity Specificity Accuracy PPV NPV
Alfatide II Visual 70.59% 90.00% 81.08% 85.71% 78.26% FDG Visual 64.71% 90.00% 78.38% 84.62% 75.00% Alfatide II + FDG Visual 82.35% 85.00% 83.78% 82.35% 85.00% Alfatide II SUV_max 76.47% 90.00% 83.78% 86.67% 81.82% Alfatide II SUV_mean 70.59% 95.00% 83.78% 92.31% 79.17% Alfatide II T/NT 76.47% 100% 89.19% 100% 83.33% FDG SUV_max 82.35% 90.00% 86.49% 87.50% 85.71% FDG SUV_mean 82.35% 90.00% 86.49% 87.50% 85.71% FDG T/NT 88.24% 85.00% 86.49% 83.33% 89.47%

There were three false negative cases for both ¹⁸F-Alfatide II and ¹⁸F-FDG. All the 3 cases belonged to luminal B subtype (Fig. 2). The other 2 false negative cases for ¹⁸F-Alfatide II were triple-negative subtype (Fig. 3). The remaining 3 false negative cases for ¹⁸F-FDG were all luminal B subtype (Fig. 4). One case of ductal carcinoma in situ was false positive for both ¹⁸F-Alfatide II and ¹⁸F-FDG (Fig. 5). The other false positive case for ¹⁸F-Alfatide II was luminal B subtype and that for ¹⁸F-FDG was HER-2 overexpressing subtype.

Semi-quantitative Assessment Findings

ROC curves of various semi-quantitative parameters are shown in Fig. 6. For both ¹⁸F-Alfatide II and ¹⁸F-FDG, the curves are located at the upper left of the chance line, indicating their strong potential for identifying ALN metastasis in breast cancer patients. However, the AUCs of ¹⁸F-Alfatide II are slightly less than those of ¹⁸F-FDG. The corresponding statistics of the ROC curves are presented in Table 3. The AUCs of ¹⁸F-Alfatide II are between 0.8 and 0.9, while those of ¹⁸F-FDG are all more than 0.9. The maximum Youden indices are close among these semi-quantitative parameters. ¹⁸F-Alfatide II T/NT has the highest Youden index (76.50%), which indicates that the parameter has the highest diagnostic accuracy. Corresponding to the maximum Youden index, each semi-quantitative parameter has its cutoff value. Based on these cutoff values, the sensitivity, specificity, accuracy, PPV and NPV values are calculated in Table 2. Although the sensitivity of each ¹⁸F-Alfatide II parameter is less than that of ¹⁸F-FDG, the specificity of the former is superior or equal to that of the latter. In particular, ¹⁸F-Alfatide II T/NT has the highest specificity (100%), accuracy (89.19%) and PPV (100%) among all these parameters. The highest sensitivity (88.24%) is for ¹⁸F-FDG T/NT, as well as the highest NPV (89.47%).

Table 3
ROC Quantitative Analysis of ¹⁸F-Alfatide II and ¹⁸F-FDG in Identifying ALN Metastasis
Parameter AUC P Cutoff value Youden index
Alfatide II SUV_max 0.812 0.001 1.095 66.50% Alfatide II SUV_mean 0.804 0.002 0.81 65.60% Alfatide II T/NT 0.851 0.000 2.5 76.50% FDG SUV_max 0.924 0.000 1.265 72.40% FDG SUV_mean 0.921 0.000 0.79 72.40% FDG T/NT 0.922 0.000 2.745 73.20%

Comparisons Among Different Groups of ALN

The SUV_max, SUV_mean and T/NT for ¹⁸F-Alfatide II between metastatic axillary lymph node (MALN) group and non-metastatic axillary lymph node (i.e. benign axillary lymph node, BALN) group are compared in Table 4, as well as those for ¹⁸F-FDG. Using any of the three parameters, MALN had significantly higher ¹⁸F-Alfatide II uptake than BALN (P < 0.05). The same result was obtained for ¹⁸F-FDG. The SUV_max, SUV_mean and T/NT for the two tracers in the primary breast tumors with MALN and BALN are also compared in Table 5. No statistically significant differences between the two groups were found (all P values were greater than 0.05).

Table 4
Comparisons of ¹⁸F-Alfatide II and ¹⁸F-FDG Uptake between MALN and BALN
Parameter MALN BALN t P
Alfatide II SUV_max 2.608 ± 2.034 0.675 ± 0.379 4.175 0.000 Alfatide II SUV_mean 1.594 ± 1.191 0.487 ± 0.230 4.075 0.000 Alfatide II T/NT 5.922 ± 4.452 1.335 ± 0.550 4.579 0.000 FDG SUV_max 4.173 ± 3.762 0.833 ± 0.796 3.879 0.000 FDG SUV_mean 2.658 ± 2.304 0.580 ± 0.490 3.941 0.000 FDG T/NT 12.348 ± 12.370 2.079 ± 1.580 3.687 0.001

Table 5
Comparisons of ¹⁸F-Alfatide II and ¹⁸F-FDG uptake between Primary Tumors with MALN and Primary Tumors with BALN.
Parameter Primary Tumors with MALN Primary Tumors with BALN t P
Alfatide II SUV_max 4.205 ± 2.186 3.563 ± 1.552 1.043 0.304 Alfatide II SUV_mean 2.521 ± 1.251 2.186 ± 0.954 0.925 0.361 Alfatide II T/NT 6.330 ± 4.015 4.719 ± 2.177 1.549 0.130 FDG SUV_max 6.927 ± 3.585 7.510 ± 5.002 0.401 0.691 FDG SUV_mean 4.230 ± 2.198 4.686 ± 3.215 0.494 0.625 FDG T/NT 7.672 ± 5.099 11.385 ± 15.809 0.926 0.361

¹⁸F-Alfatide II is a PET probe to target integrin α_vβ₃. Our previous study demonstrated the clinical usefulness of ¹⁸F-Alfatide II in breast cancer, suggesting that it is comparable to ¹⁸F-FDG for identification of breast cancer and can exert a complementary role to ¹⁸F-FDG for some subtypes (21). When using ¹⁸F-Alfatide II to detect lymph node metastases, Zhou’s study (22) showed encouraging results with the sensitivity of 100%, the specificity of 94.90% and the accuracy of 95.40% for non-small cell lung cancer patients.

In this study, visual assessment findings showed that the false negative rate of ¹⁸F-Alfatide II (5/17) was similar to that of ¹⁸F-FDG (6/17) for detecting metastatic ALN, whereas the false positive rate of ¹⁸F-Alfatide II (2/20) was about the same as that of ¹⁸F-FDG (2/20). The relatively low sensitivity (64.71%) and high specificity (90.00%) of ¹⁸F-FDG in our study were consistent with the numbers reported in previous studies (24–31). Compared with ¹⁸F-FDG, ¹⁸F-Alfatide II had the same high specificity (90.00%) and relatively higher sensitivity (70.59%). Moreover, the accuracy, PPV and NPV of ¹⁸F-Alfatide II were somewhat higher than those of ¹⁸F-FDG. Although ¹⁸F-Alfatide II was non-inferior to ¹⁸F-FDG in detecting metastatic ALN, its sensitivity (70.59%) was much lower than that reported by Zhou et al. in lung cancer patients, which was almost 100% (22). For both ¹⁸F-Alfatide II and ¹⁸F-FDG, the relatively high number of false negative cases is the main cause for the compromised sensitivity. However, combining ¹⁸F-Alfatide II and ¹⁸F-FDG together can significantly improve sensitivity and NPV, suggestive of their mutually complementary role.

For ¹⁸F-FDG, all 6 false negative cases were of luminal B subtype. Although there are still controversies on the correlation between hormonal receptor status, HER-2 overexpression and ¹⁸F-FDG uptake (32, 33), ALN without ¹⁸F-FDG foci should remain alerted for breast cancer patients of luminal B subtype. For ¹⁸F-Alfatide II, three of the five false negative cases were also luminal B subtype, which may be attributed to the small sized ALN in the three patients. The other two false negative cases of ¹⁸F-Alfatide II were triple-negative subtype. Our previous study also demonstrated that primary tumors of triple-negative subtype had the lowest ¹⁸F-Alfatide II uptake compared with the other three subtypes (21). Thus ¹⁸F-Alfatide II appears to bring about false negative results for assessing ALN of triple-negative subtype just like what we observed in assessing primary tumors. Based on our findings, ¹⁸F-Alfatide II can play a complementary role to ¹⁸F-FDG in assessing ALN of luminal B subtype, while ¹⁸F-FDG can make up for the deficiency of ¹⁸F-Alfatide II in evaluating ALN of triple-negative subtype.

According to semi-quantitative assessment findings in this study, three parameters (SUV_max, SUV_mean, T/NT) of ¹⁸F-Alfatide II showed AUCs of more than 0.8, indicating their strong potential for detecting metastatic ALN. As presented in Table 3, the optimal cutoff value is 1.095 for ¹⁸F-Alfatide II SUV_max, 0.81 for ¹⁸F-Alfatide II SUV_mean and 2.5 for ¹⁸F-Alfatide II T/NT. Although the AUCs (< 0.9) of ¹⁸F-Alfatide II are all less than those (> 0.9) of ¹⁸F-FDG, ¹⁸F-Alfatide II T/NT has the highest Youden index (76.50%), specificity (100%), accuracy (89.19%) and PPV (100%) among all these parameters. These data suggested that ¹⁸F-Alfatide II T/NT may have the potential to serve as the most important semi-quantitative parameter to be used for evaluation of ALN.

In the previous study, ¹⁸F-Alfatide uptakes in malignant lymph nodes were significantly higher than those in benign lymph nodes for non-small cell lung cancer patients (22). Our results also showed that MALN had higher ¹⁸F-Alfatide II uptake than BALN, as well as ¹⁸F-FDG uptake. These data suggested that both ¹⁸F-Alfatide II and ¹⁸F-FDG are suitable to distinguish between MALN and BALN. However, no difference was found in ¹⁸F-Alfatide II and ¹⁸F-FDG uptakes among the primary breast tumors with MALN and with BALN. Several previous studies demonstrated that the higher ¹⁸F-FDG uptake of the primary breast lesion could mean a higher incidence of ALN metastasis (8, 34–36). Other studies however revealed no significant difference between MALN and BALN in terms of primary breast mass in ¹⁸F-FDG PET/CT (37, 38), which was also found in the present study for both ¹⁸F-Alfatide II and ¹⁸F-FDG. Song et al. thought molecular subtypes should be considered as a possible factor to affect ¹⁸F-FDG uptake by primary breast cancer lesion for predicting ALN metastasis (8). Kim et al. demonstrated that ¹⁸F-FDG uptake of primary breast cancer lesion has a significant predictive value for ALN metastasis in patients with ER-positive/HER-2-negative and HER-2-positive subtypes (39). More luminal B subtype and triple-negative subtype were included in our study, which could cause no significant difference in primary breast tumors with MALN versus BALN for ¹⁸F-FDG and ¹⁸F-Alfatide II.

There are some limitations in the present study. Particularly, the number of cases is not large enough. Due to the small number of luminal A and HER-2 overexpressing subtype, the evaluation of ALN using ¹⁸F-Alfatide II in each subtype was not conducted in this study. In the future, further investigations are required to concentrate on exploring the preference of ¹⁸F-Alfatide II in assessing ALN for some certain subtypes of breast cancer.

¹⁸F-Alfatide II can be used to detect metastatic ALN like ¹⁸F-FDG with high specificity but relatively low sensitivity. Combining ¹⁸F-Alfatide II and ¹⁸F-FDG can significantly improve sensitivity and NPV. ¹⁸F-Alfatide II is insufficient for assessing ALN of triple-negative subtype but complementary to ¹⁸F-FDG for ALN of luminal B subtype. Having the highest specificity, accuracy and PPV, ¹⁸F-Alfatide II T/NT may be the most important semi-quantitative parameter for the evaluation of ALN. PET/CT can distinguish between MALN and BALN based on ¹⁸F-Alfatide II uptake of the ALN, but can’t do based on ¹⁸F-Alfatide II uptake of the primary breast tumor.

Compliance with Ethical Standards:

Conflict of Interest:

All authors declare no conflict of interest.

Ethical approval:

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent:

Informed consent was obtained from all individual participants included in the study.

Funding: This study was funded by X (grant number X).

This work was supported by the National Key Basic Research Program of China (973 program, 2014CB744504), the National Natural Science Foundation of China (81971675), the Natural Science Foundation of Jiangsu Province (BK20160610), Jiangsu Province Social Development Program (BE2017772), Jiangsu Planned Projects for Postdoctoral Research Funds (1601090C), and the National University of Singapore Start-up Fund (R-180-000-017-133, R-180-000-017-733, R-180-000-017-731).

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published 09 Feb, 2022

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18 Jan, 2021

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18F-Alfatide II for the evaluation of axillary lymph nodes in breast cancer patients: comparison with 18F-FDG

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Abstract

Figures

Introduction

Materials And Methods

Patients

PET/CT Acquisition

Image Analysis

Statistical Analysis

Results

Pathological Findings

Visual Assessment Findings

Semi-quantitative Assessment Findings

Comparisons Among Different Groups of ALN

Discussion

Conclusion

Declarations

Compliance with Ethical Standards:

Conflict of Interest:

References

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Journal Publication

Version 1