Head-to-head Analysis Of ¹⁸F-PSMA-1007 With ¹⁸F-FDG PET/CT In Prostate Cancer Intratumoral Heterogeneity And Its Clinical Significance

Objective:Prostate cancer（PC）is a disease with significant intratumoral heterogeneity,and its intratumoral heterogeneity poses a challenge for clinical diagnosis and treatment decisions,and its study can help in disease management.The purpose of this study is to investigate the intra-tumoral heterogeneity of PC based on prostate-specific membrane antigen（PSMA）and fluorodeoxyglucose（FDG）positron emission tomography（PET/CT）.The head-to-head computed tomography（PET/CT）image was used to analyze the intratumoral heterogeneity of primary prostate cancer,explore its clinical significance,and explore the possible factors influencing it through molecular pathology.Methods:Forty-five subjects with primary PC confirmed by pathological puncture were prospectively enrolled in this study,and all subjects underwent ¹⁸F-PSMA-1007 and ¹⁸F-FDG PET/CT.The prostate gland of each PC subject was divided into 6 segments based on prostate sextant segmentation.Using the maximum standard uptake value（SUVmax）of the spleen as the threshold in ¹⁸F-PSMA-1007 PET/CT and the SUVmax of the liver as the threshold in ¹⁸F-FDG PET/CT,the segments were divided into 4 PET imaging phenotypes（PSMA+/FDG-,PSMA+/FDG+,PSMA-/FDG+,PSMA-/FDG-）.The correlation between the different imaging phenotype segments and their corresponding puncture pathology Gleason score（GS）was further analyzed.The value of the different imaging phenotypes in the American joint committee on cancer（AJCC）prognostic staging group was also evaluated.A total of 128 PC puncture specimens from 29 subjects were collected for immunohistochemistry（IHC）analysis of PSMA,glucose transporter 1（Glut1）,chromogranin A（Cg A）and synaptophysin（SYN）.Results:There were 201 PC segments in 45 subjects,including 45（22.4%）PSMA+/FDG-,60（29.9%）PSMA+/FDG+,56（27.9%）PSMA-/FDG+,and 40（19.9%）PSMA-/FDG-.PSMA-/FDG+PC segments were mainly distributed in the high-grade GS group（P<0.05）,PSMA-/FDG-PC segments were mainly distributed in the low-grade GS group（P<0.05）,PSMA+/FDG+PC segments were concentrated in the mid-and high-grade GS group（P<0.05）,and PSMA+/FDG-PC segments were concentrated in the low-and mid-grade GS group（P<0.05）.From the subject-level analysis,the FDG-dominant subject group（PSMA-/FDG+）was found to have a worse prognostic staging group for AJCC than the PSMA-dominant（PSMA+/FDG-）and double-negative subject groups（PSMA-/FDG-）（P<0.05,P<0.001）.In univariate analysis,the percentage of positive punctures（b=0.045,t=4.487,P<0.001）,prostate with or without PSMA-/FDG+segments（b=2.389,t=4.618,P<0.001）,PSMA+/FDG+segments（b=1.278,t=2.123,P<0.05）,PSMA-/FDG-segments（b=-1.289,t=-2.089,P<0.05）were associated with the AJCC prognostic staging group.In multivariate analysis,the percentage of positive punctures（b=0.036,t=4.009,P<0.001）,and the presence or absence of PSMA-/FDG+segments in the prostate（b=1.910,t=4.143,P<0.001）were independent prognostic factors in the poorer AJCC prognostic staging group.IHC analysis suggested that the immunoreactive score（IRS）of PSMA,Glut1 respectively correlated with the uptake of ¹⁸F-PSMA-1007 and ¹⁸F-FDG PET/CT（P<0.05）,and FDG+PC lesions were more likely to show SYN+,a neuroendocrine-related index of PC（P<0.05）.Conclusion:The dual-tracer PET/CT imaging phenotype of primary PC correlated with GS.The FDG-dominant subject group（PSMA-/FDG+）had a worse prognostic staging group for AJCC than the PSMA-dominant（PSMA+/FDG-）and double-negative subject group（PSMA-/FDG-）.The presence of PSMA-/FDG+PC segments in the subject’s prostate was an independent adverse prognostic factor in the AJCC prognostic staging group.FDG+PC lesions correlated with PC neuroendocrine index SYN.