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PSMA and 18F-FDG PET Imaging in the Treatment of Metastatic Prostate Cancer with 223Ra: Initial Application and Experience
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摘要:
目的 分享前列腺特异性膜抗原(prostate specific membrane antigen, PSMA)和/或18F-氟代脱氧葡萄糖(18F-fluoroodexyglucose, 18F-FDG)正电子发射断层显像(positron emission tomography, PET)在前列腺癌(prostate cancer, PCa)骨转移患者氯化镭-223(radium-223 dichloride, 223Ra)治疗中的应用心得, 以期为国内开展223Ra治疗提供借鉴。 方法 本研究为描述性分析。研究对象为2021年9月-2023年1月北京协和医院因骨转移行223Ra治疗的PCa患者。记录223Ra治疗效果及患者生存状态, 并对治疗前后骨扫描及PET显像特征(包括PSMA PET和/或18F-FDG PET)进行总结。 结果 共入选9例接受不同针次223Ra治疗的PCa患者(另外2例拟行223Ra, 因基线PET显像检出存在内脏转移而排除), 包括8例转移性去势抵抗性前列腺癌患者, 1例转移性激素敏感性前列腺癌患者。9例患者共接受36针223Ra治疗, 其中6针、5针、4针、2针、1针治疗者分别为3例、1例、2例、2例、1例; 治疗中期或治疗结束时, 部分缓解1例, 病情稳定1例, 疾病进展6例, 余1例于1针223Ra治疗后转为内分泌治疗, 未进行疗效评估。截至末次随访时(2023年3月15日), 9例患者中, 死亡4例(1例死因为心力衰竭, 3例为疾病进展), 存活5例。死亡或疾病进展患者的基线PET显像所示的转移灶与骨扫描图像存在不一致性, 前者可发现更多的骨转移灶; 在治疗过程中PET显像可更精准地进行病情评估, 尤其PSMA PET显像可避免因骨闪烁现象导致治疗效果评价不准确的现象。 结论 PSMA PET和/或18F-FDG PET显像可检出内脏转移灶, 辅助临床进行223Ra治疗病例筛选, 且基线PSMA PET和/或18F-FDG PET显像特征与骨扫描结果存在不一致时, 提示223Ra治疗效果可能较差; 在治疗过程中, 相较于骨扫描, PSMA PET和/或18F-FDG PET显像(尤其PSMA PET)对疗效的评价更为准确。 Abstract:Objective To share our experience of the use of prostate specific membrane antigen (PSMA) and/or 18F-fluoroodexyglucose (18F-FDG) positron emission tomography (PET) in the setting of radium-223 dichloride (223Ra) in treatment of bone metastases of prostate cancer in order to broaden the know-ledge of application of 223Ra in China. Methods Retrospective analysis was conducted for the patients with advanced prostate cancer treated with 223Ra in Peking Union Medical College Hospital between September 2021 to January 2023.The treatment outcomes and survival status were recorded.Characteristics of bone scans and PET imaging (including PSMA PET and/or 18F-FDG PET) before and after treatment were summarized. Results Nine patients were enrolled (2 additional patients were excluded for the reason of visceral metastases confirmed by pretreatment PET imaging), among whom 8 patients had metastatic castration resistant prostate cancer and 1 had metastatic hormone-sensitive prostate cancer.In total the 9 patients received 36 doses of 223Ra, and the numbers of patients receiving 6, 5, 4, 2, and 1 doses were 3, 1, 2, 2, and 1, respectively.At the middle or end of treatment, there was 1 case of partial remission, 1 case of stable disease, 6 cases of progressive disease, and 1 case was switched to endocrine therapy after 1 shot of 223Ra treatment so that the efficacy was not evaluated.At the time of the last follow-up (March 15, 2023), among the 9 patients, 4 died (1 due to heart failure and 3 due to disease progression) and 5 survived.For patients who died or with progressive disease, there was an inconsistency between the metastases shown on baseline PET images and bone scans, with the former modality revealing more bone metastases.PET imaging especially PSMA PET was more accurate than bone scan in assessing response and could avoid bone scintillation. Conclusions PSMA PET and/or 18F-FDG PET could help detect visceral metastases and assist in patient screening.The inconsistency between baseline PET images and bone scan images suggests a worse outcome of 223Ra treatment.During the efficacy evaluation process, PSMA and/or 18F-FDG PET (especially PSMA PET) also outperforms bone scan. -
Key words:
- prostate cancer /
- radium-223 dichloride /
- prostate specific membrane antigen /
- FDG
专家点评:北京协和医院核医学科霍力教授骨骼是晚期前列腺癌常见的转移部位。骨转移将导致一系列骨相关不良事件发生，严重影响患者生活质量，是前列腺癌致死的主要原因。传统治疗方法，如手术、雄激素剥夺疗法、放射治疗(如外放射治疗或β粒子药物治疗)、镇痛及双膦酸盐类药物治疗等尚不能满足临床需求，对于骨痛症状的控制不理想。223Ra是目前国内外指南唯一推荐的存在症状性骨转移且无内脏转移的去势抵抗性前列腺癌的核素治疗药物，不仅有助于延长前列腺癌骨转移患者总生存期，延缓骨相关不良事件发生，而且镇痛效果明显，可显著改善患者生活质量。鉴于223Ra在国内的获批时间较短，相关研究较匮乏且主要集中于223Ra的有效性及安全性评估方面。本研究是国内首次探究PET显像在指导223Ra治疗中应用价值的相关研究，结果显示PSMA/18F-FDG PET显像联合骨扫描在223Ra治疗患者的病例筛选、疗效监测及预后评估中具有特殊优势，有助于优化治疗方案，提高治疗效果，同时避免了无效的医疗干预。基于本研究结果，作者首次对现行国际指南所推荐的223Ra治疗病例筛选标准提出了质疑，认为有必要将PSMA/18F-FDG PET显像纳入病例筛选体系，以辅助临床识别出对该治疗方式更敏感的人群，体现了作者团队勇于创新、敢于质疑的科学精神，值得国内外同行借鉴。作者贡献：胡桂兰主要负责PET显像检查，患者资料收集及论文撰写；李永强、纪志刚负责患者初筛与评估，并提供临床技术支持；田健负责治疗药物核查及准备工作；陈永辉、霍力辅助研究设计及论文修订。利益冲突：所有作者均声明不存在利益冲突 -
图 1 1例男性患者，59岁，确诊PCa 7年余，经手术、放化疗及内分泌治疗后出现多发骨转移，拟行223Ra治疗，基线18F-FDG PET(A、B，箭头)和PSMA PET(C、D，箭头)均提示存在肺转移及肾上腺转移，判定该患者不宜接受223Ra治疗
PCa：前列腺癌；18F-FDG：18F-氟代脱氧葡萄糖；PSMA：前列腺特异性膜抗原；PET：正电子发射断层显像；223Ra：氯化镭-223
图 2 223Ra治疗前后9例患者临床指标变化
D~G中的蓝色水平虚线代表正常参考值下限223
Ra: 同图 1；PSA：前列腺特异性抗原；ALP: 碱性磷酸酶；WBC：白细胞；RBC：红细胞；HGB：血红蛋白；PLT：血小板
图 3 病例7治疗前18F-FDG PET(A)、PSMA PET(B)示骨转移灶均明显多于骨扫描(C、D)，尤其骨盆部分(红色圆圈)，且骨扫描显示骨盆多发转移灶对示踪剂的摄取程度低，可能预示治疗效果不佳
18F-FDG、PSMA、PET：同图 1
图 4 病例9治疗前骨扫描示左侧髂骨及左侧髋臼骨转移(A、B)，其中髋臼转移灶摄取程度较低(红色箭头)，PSMA PET(C，黑色箭头)和18F-FDG PET(D，黑色箭头)示骨转移灶明显多于骨扫描；3针223Ra治疗后，骨扫描未见新增病灶(E、F)，而PSMA PET和18F-FDG PET均示原骨转移灶范围较前增大且出现新发多处骨转移灶(G、H，蓝色箭头)
18F-FDG、PSMA、PET：同图 1
图 5 病例3骨扫描示相较于治疗前(A、B), 治疗中期(C、D)时骨转移灶示踪剂摄取程度明显增高，治疗结束后较治疗前变化不明显(E、F)；相较于较治疗前(G)，治疗中期(H)及治疗结束后(I)PSMA PET显像均提示骨转移灶数量明显减少；相较于治疗前(J)，治疗中期时18F-FDG PET显像提示骨髓放射性摄取弥漫性增高(K，结合血常规结果考虑为继发性骨髓放射性摄取增高而非新增转移灶)，治疗结束后骨髓继发放射性摄取增高基本缓解(L)，骨转移灶数目明显减少，转移灶代谢活性明显减低，考虑为部分缓解
18F-FDG、PSMA、PET：同图 1
表 1 9例患者基本资料
病例编号 年龄(岁) 诊断结果 Gleason评分(分) ECOG评分(分) 病程(月) 既往治疗方式 1 63 mCRPC 4+5 1 36 RP+ADT+NAH+化疗+放疗 2 78 mCRPC 4+4 3 20 ADT+NAH 3 69 mCRPC 4+5 2 14 ADT+NAH 4 80 mCRPC / 4 24 ADT 5 65 mCRPC 4+5 2 11 ADT+NAH 6 81 mHSPC 4+4 0 7 ADT+NAH 7 87 mCRPC / 3 13 ADT+NAH 8 70 mCRPC 5+4 2 12 NAH 9 80 mCRPC 5+5 1 27 NAH+化疗 mCRPC：转移性去势抵抗性前列腺癌；mHSPC：转移性激素敏感性前列腺癌；ECOG：美国东部肿瘤协作组；RP：根治性切除术；ADT：雄激素剥夺疗法；NAH：新型内分泌药物治疗；/：无数据 
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表 2 9例患者治疗前后影像学检查情况及患者预后
病例
编号治疗
针次治疗前 治疗中期(3针后) 治疗结束后(6针后) 疗效
评价末次随访时生存状态
(开始223Ra治疗后生存时间)1 6 骨扫描+PSMA PET 骨扫描+PSMA PET 患者拒绝进一步影像学检查 PD† 存活(539 d) 2 5 骨扫描+PSMA PET 骨扫描+PSMA PET 治疗5针后因心力衰竭死亡 PD† 死亡(137 d) 3 6 骨扫描+PSMA/18F-FDG PET 骨扫描+PSMA/18F-FDG PET 骨扫描+PSMA/18F-FDG PET PR§ 存活(439 d) 4 2 骨扫描+PSMA PET 治疗2针后因PD放弃治疗 / PDζ 死亡(122 d) 5 4 骨扫描+18F-FDG PET* 骨扫描 治疗4针后因PD放弃治疗 PD† 死亡(534 d) 6 6 骨扫描*+PSMA/18F-FDG PET 骨扫描+PSMA/18F-FDG PET 骨扫描+ PSMA/18F-FDG PET SD§ 存活(329 d) 7 2 骨扫描+PSMA/18F-FDG PET 治疗2针后因PD放弃治疗 / PDζ 死亡(37 d) 8 1 骨扫描+PSMA/18F-FDG PET 治疗1针后放弃治疗 / 未评价 存活(148 d) 9 4 骨扫描*+PSMA/18F-FDG PET 骨扫描+PSMA/18F-FDG PET 治疗4针后因PD放弃治疗 PD† 存活(133 d) 223Ra、PSMA、18F-FDG、PET：同图 1；PD：疾病进展；PR：部分缓解；SD：病情稳定；*外院检查结果；†治疗中期时评价结果；§治疗结束后评价结果；ζ治疗2针时评价结果
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