Comparison of Tc-99m maraciclatide and Tc-99m sestamibi molecular breast imaging in patients with suspected breast cancer

Abstract

Background: Molecular breast imaging (MBI) performed with 99mTc sestamibi has been shown to be a valuable technique for the detection of breast cancer. Alternative radiotracers such as 99mTc maraciclatide may offer improved uptake in breast lesions. The purpose of this study was to compare relative performance of 99mTc sestamibi and 99mTc maraciclatide in patients with suspected breast cancer, using a high-resolution dedicated gamma camera for MBI. Women with breast lesions suspicious for malignancy were recruited to undergo two MBI examinations-one with 99mTc sestamibi and one with 99mTc maraciclatide. A radiologist interpreted MBI studies in a randomized, blinded fashion to assign an assessment score (1-5) and measured lesion size. Lesion-to-background (L/B) ratio was measured with region-of-interest analysis.

Results: Among 39 analyzable patients, 21 malignant tumors were identified in 21 patients. Eighteen of 21 tumors (86%) were seen on 99mTc sestamibi MBI and 19 of 21 (90%) were seen on 99mTc maraciclatide MBI (p = 1). Tumor extent measured with both radiopharmaceuticals correlated strongly with pathologic size (99mTc sestamibi, r = 0.84; 99mTc maraciclatide, r = 0.81). The L/B ratio in detected breast cancers was similar for the two radiopharmaceuticals: 1.55 ± 0.36 (mean ± S.D.) for 99mTc sestamibi and 1.62 ± 0.37 (mean ± S.D.) for 99mTc maraciclatide (p = 0.53). No correlation was found between the L/B ratio and molecular subtype for 99mTc sestamibi (r s = 0.12, p = 0.63) or 99mTc maraciclatide (r s = -0.12, p = 0.64). Of 20 benign lesions, 10 (50%) were seen on 99mTc sestamibi and 9 of 20 (45%) were seen on 99mTc maraciclatide images (p = 0.1). The average L/B ratio for benign lesions was 1.34 ±0.40 (mean ±S.D.) for 99mTc sestamibi and 1.41 ±0.52 (mean ±S.D.) for 99mTc maraciclatide (p = 0.75). Overall diagnostic performance was similar for both radiopharmaceuticals. AUC from ROC analysis was 0.83 for 99mTc sestamibi and 0.87 for 99mTc maraciclatide (p = 0.64).

Conclusions: 99mTc maraciclatide offered comparable lesion uptake to 99mTc sestamibi, in both malignant and benign lesions. There was good correlation between lesion extent and uptake measured from both radiopharmaceuticals. 99mTc maraciclatide offered a marginal (but not significant) improvement in sensitivity over 99mTc sestamibi. Our findings did not support an association between the uptake of either radiopharmaceutical and tumor molecular subtype.

Trial registration: ClinicalTrials.gov, NCT00888589.

Keywords: Breast cancer; Molecular breast imaging; Tc-99m NC100692; Tc-99m maraciclatide; Tc-99m sestamibi.

Figures

Fig. 1

Molecular breast images in the mediolateral oblique projection from a 73-year-old patient with biopsy-proven invasive lobular carcinoma (Table 1, tumor #21). At blinded review, MBI performed with 300 MBq 99mTc sestamibi (a) was interpreted as negative; MBI performed 3 days later with 300 MBq 99mTc maraciclatide (b) was interpreted as assessment category 4. The lesion extent was 9.3 cm (arrows). Final pathology revealed grade I invasive lobular carcinoma of luminal A subtype, forming a 2.5-cm mass

Fig. 2

Distribution of assessment scores in a all 78 breasts and b 21 breasts with proven breast cancer

Fig. 3

a Correlation between largest tumor extent recorded from pathology and largest tumor extent measured from 99mTc sestamibi images in 18 malignant tumors seen on MBI (r = 0.82). Open square = neoadjuvant chemotherapy, size estimated from MRI. b Correlation between largest tumor extent recorded from pathology and largest tumor extent measured from 99mTc maraciclatide images in 19 malignant tumors seen on MBI (r = 0.74). Open square = neoadjuvant chemotherapy, size estimated from MRI. c Correlation between tumor extent measured from 99mTc sestamibi images and from 99mTc maraciclatide images in 18 malignant tumors detected on both scans (r = 0.93)

Fig. 4

Molecular breast images in the mediolateral oblique projection from a 53-year-old patient with a palpable lesion that was suspicious on diagnostic mammography and scheduled for biopsy (Table 1, tumor #16). At blinded review, MBI performed with 300 MBq 99mTc sestamibi (a) was interpreted as having moderate intensity radiotracer uptake in a segmental distribution with maximum extent of 11.0 cm. An assessment of 4 was assigned. MBI performed 1 day later with 300 MBq 99mTc maraciclatide (b) was also interpreted as assessment 4 with lesion extent measuring 9.2 cm. Pathology revealed grade III invasive ductal carcinoma. Patient underwent subsequent neoadjuvant chemotherapy. Tumor extent measured on contrast-enhanced MRI prior to neoadjuvant chemotherapy was estimated at 9.2 cm

Fig. 5

Molecular breast images in the mediolateral oblique projection from a 41-year-old patient with a palpable lesion that was suspicious on diagnostic mammography and scheduled for biopsy (Table 2, benign lesion #16). At blinded review, MBI performed with 300 MBq 99mTc sestamibi (a) was interpreted as having a focal area of moderate intensity radiotracer uptake with maximum extent of 1.3 cm. An assessment of 4 was assigned. MBI performed the same day with 740 MBq 99mTc maraciclatide (b) was also interpreted as assessment 4 with lesion extent measuring 1.6 cm. Biopsy revealed necrotizing granulomatous inflammation and fibrosis

Fig. 6

a Correlation between L/B ratio measured on malignant and benign lesions from 99mTc sestamibi and 99mTc maraciclatide images (malignant, r = 0.82; benign, r = 0.96; all lesions, r = 0.87). b Correlation between L/B ratio in malignant and benign lesions from 99mTc sestamibi and 99mTc maraciclatide images measured using the 1-day and 2-day protocols (1-day protocol, r = 0.89, solid line; 2-day protocol, r = 0.85, dotted line)

Fig. 7

ROC analysis of L/B ratio comparing the sensitivity and specificity of 99mTc sestamibi and 99mTc maraciclatide images. The AUC was 0.83 and 0.87 for 99mTc sestamibi and 99mTc maraciclatide respectively (p = 0.64)

Fig. 8

Distribution of L/B ratios by molecular subtype in the 20 known invasive cancers for 99mTc sestamibi (rs = 0.12, p = 0.63) and 99mTc maraciclatide (rs = −0.12, p = 0.64)