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

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.

68Ga-Pentixafor PET/CT Demonstrating In Vivo CXCR4 Receptor Overexpression in Rare Lung Malignancies: Correlation with Histologic and Histochemical Findings

“…A positive correlation was found between 68 Ga-pentixafor splenic uptake and platelet or leukocyte counts in lung cancer and neuroendocrine tumors, suggesting that splenic uptake might play a role in systemic immunity or inflammation (18). We previously reported that uptake of 68 Ga-pentixafor in SCLC patients was higher than in NCSLC and other lung cancer variants and that the uptake varied as a function of CXCR4 receptor density (11,14). However, the pattern of uptake and the in vivo evidence of CXCR4 expression in rare lung malignancies have not been studied before.…”

“…According to the available literature, noninvasive imaging of CXCR4 expression in SCLC is feasible, and 68 Ga-pentixafor as a novel PET tracer might serve as a readout for confirming the CXCR4 expression (20). Watts et al reported that 68 Ga-pentixafor uptake denoting CXCR4 expression is higher in SCLC than NSCLC patients (11,14). Evaluation of CXCR4 expression is a prerequisite for potential CXCR4-directed radiotherapies and chemotherapies in lung cancer and especially in SCLC, which has higher CXCR4 expression compared with all other variants of lung cancer.…”

“…It has recently been reported that 68 Ga-pentixafor PET/CT shows high tumor uptake in patients with lung cancer (SCLC and NSCLC), glioblastoma multiforme, and multiple myeloma. This tracer exhibited strong affinity and specificity for the in vivo localization and imaging of CXCR4 receptors in these malignancies (11,(14)(15)(16).…”