Non-invasive visualization of tumor infiltrating lymphocytes in patients with metastatic melanoma undergoing immune checkpoint inhibitor therapy: a pilot study.
Non-invasive visualization of tumor infiltrating lymphocytes in patients with metastatic melanoma undergoing immune checkpoint inhibitor therapy: a pilot study.
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DOI：
10.18632/oncotarget.25666
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发表时间：
2018-07-13
期刊：
影响因子：
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通讯作者：
Signore A
中科院分区：
文献类型：
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作者：
Markovic SN;Galli F;Suman VJ;Nevala WK;Paulsen AM;Hung JC;Gansen DN;Erickson LA;Marchetti P;Wiseman GA;Signore A
在免疫治疗过程的早期，由于肿瘤浸润TILs，经常出现肿瘤肿块的短暂扩大（假性进展）。目前的临床成像方式不能区分伪进展和真正的肿瘤进展。因此，患者通常要多接受4-8周的治疗以确认疾病进展。核医学为免疫细胞成像提供了可能，并有可能区分假进展和进展。我们在接受ipilimumab （IPI）或pembrolizumab （PEMBRO）治疗的转移性黑色素瘤患者中进行了一项初步研究，以评估用99mTc-白细胞介素-2 （99mTc- hynici - il2）进行SPECT/CT成像检测til并区分真进展和假进展的安全性和可行性。在治疗前后分别进行扫描。标记后，纯化99mTc-HYNIC-IL2，用10 mL 5%葡萄糖和0.1%人血清白蛋白稀释。在入组的5名患者（2名接受IPI治疗，3名接受PEMBRO治疗）中，2名患者因3级结肠炎（1名患者）或出现IPI引起的多种毒性后患者拒绝（1名患者）而停止IPI治疗，未能完成第二次扫描。在第一次扫描后，一名患者报告有1级瘙痒和1级疼痛。没有其他毒性归因于放射性药物输注的报道。在治疗前和治疗后12周，99mTc-IL2显像可以显示转移灶，肿瘤大小与99mtc - hyic - il2摄取呈正相关。这项初步研究的结果证明了99mTc-IL2成像的安全性和可行性，并在未来的研究中提出了一些假设。
Early in the course of immunotherapy there is frequently a transient enlargement of tumor masses (pseudo-progression) due to tumor infiltration by TILs. Current clinical imaging modalities are not able to distinguished pseudo-progression from true tumor progression. Thus, patients often remain on treatment 4-8 weeks longer to confirm disease progression. Nuclear medicine offers the possibility to image immune cells and potentially discriminate pseudo-progression and progression. We conducted a pilot study in patients with metastatic melanoma receiving ipilimumab (IPI) or pembrolizumab (PEMBRO) to assess safety and feasibility of SPECT/CT imaging with 99mTc- interleukin-2 (99mTc-HYNIC-IL2) to detect TILs and distinguish between true progression from pseudo- progression. Scans were performed prior to and after 12w treatment. After labelling,99mTc-HYNIC-IL2 was purified and diluted in 10 mL of 5% glucose with 0.1% human serum albumin. Of the 5 patients (2 treated with IPI and 3 with PEMBRO) enrolled, two failed to complete the second scan as they discontinued IPI due grade 3 colitis (1 patient) or patient refusal after developing multiple toxicities attributed to IPI (1 patient). Following the first scan, one patient reported to have a grade 1 pruritus with grade 1 pain. No other toxicities attributed to the radiopharmaceutical infusion were reported. Metastatic lesions could be visualized by 99mTc-IL2 imaging and there was positive correlation between size and 99mTc-HYNIC-IL2 uptake, both before and after 12 weeks of therapy. The results of this pilot study demonstrate the safety and feasibility of 99mTc-IL2 imaging and has led to a number of hypotheses to be tested in future studies.