68Ga-MY6349 PET/CT Outperforms FDG in Breast Cancer
Key Takeaways
- In a prospective paired-imaging breast cancer cohort in China, 68Ga-MY6349 PET/CT detected more malignant lesions and yielded fewer false positives than 18F-FDG PET/CT.
- 68Ga-MY6349 PET/CT identified all confirmed primary breast tumors and outperformed both 18F-FDG PET/CT and ultrasound for primary-tumor detection.
- Incorporating 68Ga-MY6349 findings upgraded tumor-node-metastasis staging in 20% of patients undergoing initial staging and changed management in 12% of those undergoing restaging.
- In an exploratory triple-negative breast cancer series treated with sacituzumab tirumotecan, early changes in 68Ga-MY6349 uptake tracked with later response patterns over 6 months.
At the First Affiliated Hospital of Xiamen University in China, investigators prospectively enrolled 76 patients and analyzed 73 with pathologically confirmed breast cancer from December 2024 through April 2025. All underwent paired 68Ga-MY6349 PET/CT and 18F-FDG PET/CT within 1 week, and 2 board-certified nuclear medicine physicians interpreted the scans while blinded to clinical information, pathology, and the alternate tracer study. Semiquantitative assessment included maximum standardized uptake value (SUVmax) and tumor-to-background ratio (TBR), with up to 10 lesions assessed in metastatic disease. Reference standards were histopathology for treatment-naive disease, at least 6 months of clinical and imaging follow-up for restaging lesions, and contrast-enhanced magnetic resonance imaging (MRI) for brain lesions. Treatment decisions were recorded before and after 68Ga-MY6349 PET/CT; preliminary serial imaging was also reported in 3 patients with triple-negative breast cancer (TNBC) receiving sacituzumab tirumotecan from an ongoing separate response-assessment study at the same center.
In the prospective paired PET/CT comparison of 68Ga-MY6349 and 18F-FDG in breast cancer, 68Ga-MY6349 detected 564 of 600 malignant lesions versus 436 of 600 with 18F-FDG PET/CT, with 2 versus 40 false positives. Overall median SUVmax was 5.9 [3.6-8.6] with 68Ga-MY6349 versus 4.1 [2.5-7.2] with 18F-FDG, and median TBR was 6.0 [3.6-9.6] versus 3.4 [2.1-6.7], both P < 0.001. Lesion conspicuity was especially favorable in lymph-node and metastatic lesions.
For primary disease, 68Ga-MY6349 identified all 48 pathologically confirmed breast tumors, compared with 38 detected by 18F-FDG PET/CT and 40 by ultrasound. Nodal and distant metastatic detection was also higher, including 213 of 224 nodal metastases versus 166 of 224, with no false-positive nodal findings for 68Ga-MY6349 versus 36 for 18F-FDG PET/CT. Tumor-node-metastasis stage was upgraded in 20% of patients undergoing initial staging, treatment was modified in a subset of that group, and management changed in 12% of patients undergoing restaging after additional lesions or corrected false-positive findings were incorporated.
Because the study was conducted at a single center, included modest numbers within molecular subtypes, and relied on follow-up imaging and clinical assessment rather than uniform tissue confirmation for many restaging determinations, subgroup and restaging interpretations remain limited. Lesion-level correlations between tracer uptake and Trop2 H-scores were not evaluated in this cohort. The tracer missed 36 malignant lesions, which the authors linked to small lesion size, partial-volume effects, or intertumoral heterogeneity in Trop2 expression. Uptake and contrast advantages appeared most pronounced in luminal B human epidermal growth factor receptor 2 (HER2)-negative disease and TNBC, while serial 68Ga-MY6349 imaging in 3 TNBC cases showed early uptake changes after 2 cycles that tracked with later response patterns over 6 months; those observations were exploratory.
Investigators concluded that 68Ga-MY6349 PET/CT was superior to 18F-FDG PET/CT for primary and metastatic breast cancer diagnosis in this cohort, while the serial-response observations in TNBC remained preliminary and require larger prospective validation.
Clinician Questions
How were breast cancer lesions verified in the 68Ga-MY6349 versus 18F-FDG PET/CT comparison?
For treatment-naive breast cancer, lesion verification relied on histopathology; for restaging lesions, verification relied on at least 6 months of clinical and imaging follow-up; and contrast-enhanced MRI served as the reference standard for brain lesions, so restaging confirmation was not uniformly histopathologic.
Which breast cancer subtypes appeared to show the strongest 68Ga-MY6349 uptake advantage over 18F-FDG?
The strongest reported uptake and contrast advantages for 68Ga-MY6349 over 18F-FDG were in luminal B HER2-negative breast cancer and TNBC, although each molecular subgroup was small and subtype-specific interpretation remains limited.
What factors were linked to malignant lesions missed by 68Ga-MY6349 PET/CT in breast cancer?
The authors linked missed malignant breast cancer lesions on 68Ga-MY6349 PET/CT mainly to small lesion size, possible partial-volume effects, and intertumoral heterogeneity in Trop2 expression.
What did the exploratory serial 68Ga-MY6349 scans show during sacituzumab tirumotecan treatment in TNBC?
In 3 patients with TNBC receiving sacituzumab tirumotecan, 68Ga-MY6349 uptake changes after 2 treatment cycles paralleled later 6-month outcomes, with declining uptake accompanying later complete response in one case and rising uptake accompanying progression in two cases; the authors presented those observations as preliminary.