68Ga-Pentixafor PET/CT imaging for in-vivo CXCR4 receptor mapping in different lung cancer histologic sub-types: Correlation with quantitative receptors’ density by immunochemistry techniques

Abstract

Abstract Purpose In-vivo CXCR4 receptor quantification in different lung cancer (LC) sub-types using 68Ga-Pentixafor PET/CT and correlation with quantitative CXCR4-receptors’ tissue density by immunochemistry analyses. Methods 68Ga-Pentixafor PET/CT imaging was performed prospectively in 94 (77M: 17F, mean age 60.15 ± 10.12 yrs) LC patients. CXCR4 receptors’ expression was estimated in all the patients on lung tissue by immunohistochemistry (IHC) and FACS analyses. SUVmax on PET, Intensity score on IHC and Mean fluorescence Index (MFI) on FACS analyses were measured. Results 75/94 (79.8%) cases had NSCLC, 14 (14.9%) had SCLC and 5 (5.3%) had lung NETs. All LC types showed increased CXCR4 expression on PET (SUVmax) and FACS (MFI). However, both these parameters (mean SUVmax = 10.30 ± 5.0; mean MFI = 349.0 ± 99.0) were significantly (p = 0.005) higher in SCLC as compared to NSCLC and lung NETs. PET SUVmax in adenocarcinoma (n = 16) were 8.00 ± 1.9 which was significantly (p = 0.003) higher than in squamous cell carcinoma (n = 54; 6.2 ± 2.15) and NOS (n = 5; 5.8 ± 1.5) subtypes of NSCLC. A significant correlation (r = 0.697; p = 001) was seen between SUVmax and MFI values in squamous cell NSCLC as well as in NSCLC-adenocarcinoma (r = 0.538, p = 0.031) which supports the specific uptake of 68Ga-Pentixafor by CXCR4 receptors. However, this correlation was not significant in SCLC (r = 0.435, p = 0.121) and NET (r = 0.747,p = 0.147) which may be due to the small sample size. 68Ga-Pentixafor PET/CT provided good sensitivity (85.7%) and specificity (78.1%) for differentiating SCLC from NSCLC (ROC cut-off SUVmax= 7.24). Almost similar sensitivity (87.5%) and specificity (71.4%) were observed (ROC cut-off SUVmax= 6.67) for differentiating adenocarcinoma and squamous cell variants of NSCLC. Conclusion Higher CXCR4 expression was seen in SCLC as compared to NSCLC and NETs on 68Ga-Pentixafor PET imaging. The findings may potentially supplement the existing data for inclusion and expanding CXCR4 -based radioligand therapies in LC beyond haematological malignancies.