Y. Luo1,2, S. Wang3, K. Zhao3, J. Liu3, and J. Yu4; 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 2Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China, 3Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, 4Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
Purpose/Objective(s): Molecular subtyping of small cell lung cancer (SCLC) provides important implications for prognostic relevance and treatment guidance. In this prospective work, we explore the feasibility of a novel positron emission tomography (PET) tracer targeting C-X-C-chemokine-receptor-type-4 (CXCR4) in classifying different subtypes of SCLC. Materials/
Methods: 22 patients with SCLC confirmed by pathology were included in this work. Conventional IHC staining of achaete-scute homologue 1 (ASCL1), neurogenic differentiation factor 1 (NeuroD1) and POU class 2 homeobox 3 (POU2F3) was performed on their biopsy samples. [18F] AlF-NOTA-QHY-04 PET/CT imaging parameters were evaluated, including maximum, mean and peak standard uptake values (SUVmax, SUVmean and SUVpeak). Tumor-to-normal ratios of tracer uptake in primary lesions based on SUVmax were also calculated, denoted as T/NT (T/NTlung and T/NTblood). These parameters were used to compare differences between primary and metastatic lesions of subsets. Results: According to the prominent IHC expression of the 22 patients’ specimens, the molecular subtypes of SCLC were SCLC-A (ASCL1, n=13), SCLC-N (NEUROD1, n=2), SCLC-P (POU2F3, n=4) and SCLC-I (inflamed, n=3). Parameters including SUVmax, SUVmean, SUVpeak, T/NTblood and T/NTlung of primary lesions didnt show significant difference among four subtypes. In neuroendocrine (NE) group including SCLC-A and SCLC-N, SUVmean of lymph node metatases were significantly higher in SCLC-N than SCLC-A (P<0.05), no difference in non-NE group. Meanwhile, SUVmax, SUVmean and SUVpeak of lymph node metatases were all significantly higher in SCLC-N than SCLC-P (all P</em><0.05), and SUVmax was significantly higher in SCLC-N than SCLC-I (P<0.05). Parameters of primary tumor were found higher in NE group than non-NE group such as SUVmax (8.165±2.289 v.s 6.3401±1.294, P=0.0251) and T/NTlung (12.900±4.028 v.s 9.026±11.980, P= 0.0268). In metastases, no difference was observed in all parameters between NE and non-NE groups. The receiver operating characteristics (ROC) analysis demonstrated that the cutoff value of SUVmax (Area under curve, AUC=0.800) and T/NTlung (AUC=0.819) of primary lesions were 6.28 and 8.625. These parameters had high sensitivity, specificity and accuracy in distinguishing non-NE and NE group. Conclusion: Our preliminary findings indicated that CXCR4-directed PET imaging may allow noninvasive distinction of different subtypes of SCLC.