Potential of C-X-C-Chemokine-Receptor-Type-4-Directed PET/CT Using [¹⁸F]AlF-NOTA-QHY-04 in Identifying Molecular Subtypes of Small Cell Lung Cancer.

Abstract

Objective: Molecular subtyping of small-cell lung cancer (SCLC) has major implications for prognostic relevance and treatment guidance. This study aimed to explore the feasibility of a novel tracer targeting C-X-C-chemokine-receptor-type-4 (CXCR4) for distinguishing different SCLC subtypes.

Materials and methods: Thirty-five patients with pathologically confirmed SCLC were enrolled in this prospective study. Immunohistochemical staining was performed to classify the molecular subtypes into SCLC-A, SCLC-N, SCLC-P, and SCLC-I. [¹⁸F]AlF-NOTA-QHY-04 PET/CT parameters were obtained, including the maximum, mean, and peak standard uptake values (SUV_max, SUV_mean, and SUV_peak, respectively) and the ratios of tumors (T) and normal tissues (NT) based on the SUV_max (T/NT). These parameters were compared among the molecular subtypes. A receiver operating characteristic (ROC) curve was used to analyze the performance of the parameters for distinguishing SCLC-N from other subtypes and neuroendocrine (NE) subtypes (SCLC-A and SCLC-N) from non-NE subtypes (SCLC-P and SCLC-I).

Results: The molecular subtypes were SCLC-A (n = 17), SCLC-N (n = 6), SCLC-P (n = 7), and SCLC-I (n = 5). The SCLC-N subtype exhibited significantly higher uptake in both primary tumors and lymph node metastases than the other three subtypes (P < 0.05). When SCLC-N was compared with the other three subtypes combined (referred to as "other SCLCs"), all parameters were significantly higher in the SCLC-N group (P < 0.05). ROC analysis showed that these parameters had high accuracy in distinguishing SCLC-N from other SCLCs (area under ROC curve: 0.868-0.948 for primary tumors and 0.783-0.888 for lymph node metastases). Compared with the non-NE group, the SUV_max, SUV_mean, and T/NT_lung were significantly higher in the NE group for primary tumors. ROC analysis showed moderate accuracy in distinguishing between the NE and non-NE groups (ROC area: 0.692-0.786 for primary tumors and 0.692-0.815 for lymph node metastases).

Conclusion: Our preliminary findings indicate that CXCR4-directed PET/CT imaging using [¹⁸F]AlF-NOTA-QHY-04 may differentiate between SCLC-N and other molecular subtypes and between NE and non-NE subtypes of SCLC.