Lerwine Harry

Background: Breast cancer (BC) frequently disseminates to bone. Technetium 99m methylene diphosphonate bone scintigraphy (^99m Tc‐MDP bone scintigraphy) is utilized in the staging work‐up. In detecting lytic bone lesions, bone marrow and soft tissue metastases, 2‐deoxy‐2[fluorine 18] fluoro‐D‐glucose positron emission tomography/computed tomography scan (¹⁸F‐FDG PET/CT scans) is superior. We compared bone metastases (BM) detection in both imaging modalities, and its impact on patient management. Method: One hundred BC patients underwent ¹⁸F‐FDG PET/CT scan, and ^99m Tc‐MDP bone scintigraphy performed within a maximum of six weeks of each other, between January 2017 and September 2024. Comparison based on lesion‐by‐lesion analysis. Changes in stage and management recorded. Results: The median patient age was 55 years. ^99m Tc‐MDP bone scintigraphy detected 243 BM and ¹⁸F‐FDG PET/CT scans detected 421 BM. Stage and management upgrades, secondary to detected BM, were seen in 22 patients for each imaging modality. ¹⁸F‐FDG PET/CT scans additionally detected 5 patients with unsuspected, isolated soft tissue metastases, all resulting in stage and management change (p18F‐FDG PET/CT scan and ^99m Tc‐MDP bone scintigraphy demonstrated the ability to detect BM in an equivalent number of patients. However, ¹⁸F‐FDG PET/CT scan proved superior in overall metastatic assessment, particularly in identifying additional BM and concomitant soft tissue metastases. This broader disease characterization translated into significantly higher rate of management modification compared with ^99m Tc‐MDP bone scintigraphy. Contribution: A proposed revision of current BC guidelines reflecting ¹⁸F‐FDG PET/CT scan’s validated diagnostic superiority, will reduce financial burden whilst improving patient management and compliance.

Background. CXCR4 is a chemokine receptor that is frequently overexpressed in invasive breast cancer and plays a major role in tumor proliferation, aggressiveness and metastasis. The aim of this prospective study was to establish the value of CXCR4-directed PET imaging in patients with breast cancer using the novel CXCR4-targeted PET probe ⁶⁸Ga-Pentixafor by comparing it with ¹⁸F-FDG PET/CT (n = 40). Materials and methods. In this prospective cross-sectional study, fifty-one patients with breast cancer aged 36–81 (median (Q1-Q3) 51 (42.5–63)), n = 47 (92%) with initially diagnosed and n = 4 (8%) patients with recurrent breast cancer, underwent CXCR4-targeted PET imaging using ⁶⁸Ga-Pentixafor. Maximum standardized uptake values (SUVmax), total lesion glycolysis (TLG) or total lesion uptake (TLU), metabolic tumor volume (MTV) and tumor-to-background ratios (TBR) of tumor lesions were measured and correlated with pathological prognostic factors, molecular subtypes and CXCR4 immunohistochemistry (IHC) staining. ¹⁸F-FDG PET/CT images were available in 40 of 51 cases (82%) and were compared semi-quantitatively. The patients were followed up for a median of 11 months (range 4–80 months) to determine whether CXCR4 expression correlated with survival. Results. ⁶⁸Ga-Pentixafor-PET/CT was visually positive in 49/51 (96%) of the cases; in addition, [¹⁸F]FDG demonstrated a higher SUVmax compared to ⁶⁸Ga-Pentixafor. The mean SUVmax was 7.26 ± 2.84 and 18.8 ± 9.1 for ⁶⁸Ga-Pentixafor and [¹⁸F]FDG, respectively. Thirty-seven percent (18/51) of patients had triple-negative breast cancer and 25/51 (49%) had estrogen receptor (ER+) disease. There was a statistically significant correlation between tumor grade, proliferative index (Ki-67) and SUVmax obtained from ⁶⁸Ga-Pentixafor PET p = 0.002. There was no correlation between the SUVmax obtained from ⁶⁸Ga-Pentixafor and PET molecular subtypes, estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status; however, triple-negative breast cancers had more avid ⁶⁸Ga-Pentixafor accumulation compared to luminals A and B. The median (Q1–Q3) ⁶⁸Ga-Pentixafor TLU was significantly higher in HIV-positive (376 (219–881)) compared to HIV-negative (174 (105–557)) breast cancer patients. Conclusions. In conclusion, ⁶⁸Ga-Pentixafor had a sensitivity of 96% and a specificity of 100% for detecting primary breast cancer; in addition, ⁶⁸Ga-Pentixafor exhibited significantly higher uptake in patients with higher tumor grade, high proliferative index and triple-negative breast cancer (TNBC), as well as HIV-infected breast cancer patients, highlighting the potential clinical utility and prognostic role of CXCR4-targeted PET imaging in aggressive breast cancer. Notably, ⁶⁸Ga-Pentixafor complements ¹⁸F-FDG by detecting more metastasis in the brain and the skull where FDG has limitations, while ¹⁸F-FDG remains superior for detecting skeletal metastasis. Future research should further explore the potential of CXCR4-targeted PET imaging in selecting patients with triple-negative breast cancer and high-grade breast cancer who may benefit from CXCR4-targeted therapies, particularly in the context of HIV co-infection.