RT Journal Article SR Electronic T1 [68Ga]Pentixafor PET/CT imaging in cervical cancer, a comparison with [18F]FDG JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 242218 OP 242218 VO 65 IS supplement 2 A1 Hadebe, Bawinile A1 Nxasana, Thembelihle A1 Harry, Lerwine A1 Patel, Maryam A1 Ndlovu, Nontobeko A1 Msimang, Mpumelelo A1 Sathekge, Mike A1 Masikane, Siphelele A1 Gabela, Lerato A1 Harry, Lerwine A1 Vorster, Mariza YR 2024 UL http://jnm.snmjournals.org/content/65/supplement_2/242218.abstract AB 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.