Abstract
242218
Introduction: CXCR4 is overexpressed in cervical cancer and its expression is associated with poorer prognosis and resistance to chemoradiation, however there is limited literature on the application of CXCR4 PET/CT imaging in cervical cancer. The aim of this study was to assess the diagnostic performance of CXCR4-directed PET imaging in patients with cervical carcinoma using the novel PET probe [68Ga]Pentixafor compared to [18F]FDG and CXCR4 immunohistochemistry staining.
Methods: Patients with primarily diagnosed locally advanced cervical cancer underwent [68Ga]Pentixafor-PET/CT. Images were analysed visually and semi-quantitatively for CXCR4 expression and standardized uptake values(SUVmax), total lesion uptake (TLU), metabolic tumour volume (MTV) and tumour-to-liver background ratio (TBR) and gluteal muscle ratio (TMR) of tumour lesions were measured and correlated with patient survival. 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG, and immunohistochemistry served as standards of reference.
Results: Fifteen histologically proven cervical cancer patients (mean age 46±13) were included. [68Ga]Pentixafor-PET/CT was visually positive 9/15 (60%) cases, however [18F]FDG PET demonstrated higher SUVmax in all patients compared to [68Ga]Pentixafor PET. On a lesion-based analysis [68Ga]Pentixafor detected 37 lesion and [18F]FDG detected 68 lesions. The SUVmax and SUVmean were 6.2 ± 1.45 and 3.1 ± 0.82, TLU 390±349 , MTV 121±101 and TBRand TMR was 2.1± 0.5 and 6.0±2.6, respectively for [68Ga]Pentixafor. The SUVmax and SUVmean were 19.9 ± 12.4 and 10.6± 7.1, TLG 1292 ±1623, MTV 104±105 TBR 6.4 ± 4.1 and TMR21 ± 15.5, respectively for [18F]FDG.14/15 (93%) patients had squamous cell carcinoma (SCC), and only one patient had adenocarcinoma (7%),10/15 (66%) were HIV positive (Table 1). Eight of the 15 patients (53%) had demised at the time of the analysis. There was no correlation between the SUVmax obtained from 68Ga-Pentixafor PET and tumour differentiation, HIV statuus or stage of disease. The [68Ga]Pentixafor PET TLU and MTV were higher among the patients who demised 501±455 vs 264±169 and 143±134 vs 98.0±59.5 respectively compared to the patients who were alive at the time of analysis although this did not reach statistical significance p=0.218. In addition, a poorer performance status (higher ECOG score) correlated with more intense [68Ga]Pentixafor uptake. Fig 1 displays [18F]FDG (top panel) and [ 68Ga]Pentixafor (bottom panel) images of a 53-year-old female with invasive SCC of the cervix.[ 68Ga]Pentixafor images show mild uptake in the primary lesion SUVmax 6.3 compared to [18F]FDG SUVmax 18.8 (arrowhead), 4.82 vs 7.48 in the metastatic lung lesion (thick arrow)and 3.18 vs 7.28 para-aortic lymph node (small arrow). CXCR4 staining was strongly positive, intensity +++ and 60% of the tumour cells stained positive. Fig 2 displays [18F]FDG and [68Ga]Pentixafor PET/CT images of a 58-year-old female with moderately differentiated SCC of the cervix. There is more intense uptake on [18F]FDG vs [68Ga]Pentixafor SUVmax 22.47 vs 7.18. [18F]FDG further detected pelvic lymph node metastasis which were not seen on [ 68Ga]Pentixafor.
Conclusions: Our preliminary results show that CXCR4-directed PET imaging is feasible in cervical cancer; however, tracer accumulation is significantly lower on [68Ga]Pentixafor compared to [18F]FDG PET/CT. There was a positive correlation between [68Ga]Pentixafor TLU, MTV and survival although this did not reach statistical significance. Based on these results, CXCR4-targeted PET imaging does not seem to be suitable diagnostic tool for cervical cancer imaging but may have a role in predicting survival in cervical cancer. Future CXCR4 targeting imaging studies should investigate whether this modality might be useful in selecting cervical cancer patients eligible for therapies targeting CXCR4.