First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14—a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging
First in Human Evaluation and Dosimetry Calculations for Peptide 124I-p5+14—a Novel Radiotracer for the Detection of Systemic Amyloidosis Using PET/CT Imaging
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首次对肽 124I-p5 14-a 新型放射性示踪剂进行人体评估和剂量计算，用于使用 PET/CT 成像检测系统性淀粉样变性
DOI：
10.1007/s11307-021-01681-2
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发表时间：
2022
影响因子：
3.1
通讯作者：
Julian, Ryan R.
中科院分区：
文献类型：
--
作者：
Wall, Jonathan S.;Martin, Emily B.;Endsley, Aaron;Stuckey, Alan C.;Williams, Angela D.;Powell, Dustin;Whittle, Bryan;Hall, Sarah;Lambeth, Tyler R.;Julian, Ryan R.
目的淀粉样变的准确诊断仍然是一个重大的临床挑战和未满足的患者需求。用碘-124放射性标记的淀粉样蛋白反应肽p5+14已被开发用于PET/CT成像检测淀粉样蛋白。在一项首次人体评估中，124i -p5+14肽在系统性淀粉样变性患者中的剂量学和组织分布。在此，我们报告了前三名轻链相关（AL）淀粉样变性患者的剂量学和动态分布。放射性示踪剂在一项单点、开放标签的1期研究（NCT03678259）中进行评估。前3例患者接受单次静脉输注124i -p5+14肽（≤37 MBq）。在给药后48 h进行连续PET/CT成像。剂量测定作为每个患者的主要终点，并计算性别平均平均值。通过全血放射性测量和基于器官的时间活动数据估计药代动力学参数。最后，我们通过视觉评估了放射性示踪剂在主要器官中的生物分布，并与临床评估的器官受累情况进行了比较。结果124i -p5+14输注耐受良好，在心脏、肾脏、肝脏、脾脏、胰腺和肺中迅速吸收。性别平均全身有效辐射剂量估计为0.23（±0.02）mSv/MBq，通过肾脏和胃肠道途径消除放射性。全血消除（21.9±7.6 h） t1/2。基于器官的活性浓度测量表明，AUClasttissue:blood ratio通常与预期的淀粉样蛋白存在相关。在4/5的临床疑似器官中观察到肽摄取，如医疗记录所述，以及该人群中通常与淀粉样变性相关的6个解剖部位。结论肽124i -p5+14在全身性AL患者中迅速分布到与淀粉样蛋白存在一致的解剖部位。本队列中建立的剂量学估计对于全身PET/CT成像是可以接受的。药代动力学参数是不均匀的，与示踪剂在淀粉样蛋白室的摄取一致。124i -p5+14的PET/CT成像可促进多器官系统淀粉样蛋白的无创检测。
PurposeAccurate diagnosis of amyloidosis remains a significant clinical challenge and unmet need for patients. The amyloid-reactive peptide p5+14 radiolabeled with iodine-124 has been developed for the detection of amyloid by PET/CT imaging. In a first-in-human evaluation, the dosimetry and tissue distribution of124I-p5+14 peptide in patients with systemic amyloidosis. Herein, we report the dosimetry and dynamic distribution in the first three enrolled patients with light chain-associated (AL) amyloidosis.ProceduresThe radiotracer was assessed in a single-site, open-label phase 1 study (NCT03678259). The first three patients received a single intravenous infusion of124I-p5+14 peptide (≤37 MBq). Serial PET/CT imaging was performed during the 48 h post-infusion. Dosimetry was determined as a primary endpoint for each patient and gender-averaged mean values were calculated. Pharmacokinetic parameters were estimated from whole blood radioactivity measurements and organ-based time activity data. Lastly, the biodistribution of radiotracer in major organs was assessed visually and compared to clinically appreciated organ involvement.ResultsInfusion of the124I-p5+14 was well tolerated with rapid uptake in the heart, kidneys, liver, spleen, pancreas, and lung. The gender-averaged whole-body effective radiation dose was estimated to be 0.23 (± 0.02) mSv/MBq with elimination of the radioactivity via renal and gastrointestinal routes. The whole blood elimination t1/2of 21.9 ± 7.6 h. Organ-based activity concentration measurements indicated that AUClasttissue:blood ratios generally correlated with the anticipated presence of amyloid. Peptide uptake was observed in 4/5 clinically suspected organs, as noted in the medical record, as well as six anatomic sites generally associated with amyloidosis in this population.ConclusionPeptide124I-p5+14 rapidly distributes to anatomic sites consistent with the presence of amyloid in patients with systemic AL. The dosimetry estimates established in this cohort are acceptable for whole-body PET/CT imaging. Pharmacokinetic parameters are heterogeneous and consistent with uptake of the tracer in an amyloid compartment. PET/CT imaging of124I-p5+14 may facilitate non-invasive detection of amyloid in multiple organ systems.
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影响因子：
3.7
作者：
Stats, Miriam A.;Stone, James R.
通讯作者：
Stone, James R.
哈佛医学院/布莱根妇女医院（美国）
DOI：
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发表时间：
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期刊：
影响因子：
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作者：
通讯作者：
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影响因子：
9.8
作者：
Barrett, PHR;Bell, BM;Foster, DM
通讯作者：
Foster, DM
系统性淀粉样变性的影像学。
影响因子：
6.7
作者：
S. Sachchithanantham;A. Wechalekar
通讯作者：
A. Wechalekar
DOI：
10.1007/s00259-018-3995-2
发表时间：
2018-07
影响因子：
9.1
作者：
Wagner T;Page J;Burniston M;Skillen A;Ross JC;Manwani R;McCool D;Hawkins PN;Wechalekar AD
通讯作者：
Wechalekar AD