提高对比度和检测能力：[Co]Co-DOTATATE 与 [Cu]Cu-DOTATATE 和 [Ga]Ga-DOTATATE 的成像比较。
Improving Contrast and Detectability: Imaging with [Co]Co-DOTATATE in Comparison with [Cu]Cu-DOTATATE and [Ga]Ga-DOTATATE.
机构信息
PET Unit, Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark; and.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
出版信息
J Nucl Med. 2020 Feb;61(2):228-233. doi: 10.2967/jnumed.119.233015. Epub 2019 Sep 13.
PET imaging at late time points after injection may allow tracer clearance from normal tissue and hence improve image contrast and detectability. Co is a promising isotope with high positron yield and a long half-life suitable for imaging at delayed time points. Here, we compared the 3 radioconjugates [Ga]Ga-DOTATATE, [Cu]Cu-DOTATATE, and [Co]Co-DOTATATE by PET/CT imaging in NOD-SCID mice bearing subcutaneous somatostatin receptor-expressing AR42J tumors. Co and Cu were produced by the Fe(d,n)Co and Ni(p,n)Cu nuclear reactions, whereas Ga was obtained from a Ge/Ga generator. Co and Cu were labeled with DOTATATE by heating in a sodium acetate buffer and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid buffer, respectively. AR42J tumor-bearing mice were dynamically scanned 0-1 h after injection. For Cu and Co, additional imaging was also performed at late time points after 4 and 24 h. Dose calculations were based on a known biodistribution. The cumulated disintegrations in each organ were calculated by integration of a fitted exponential function to the biodistribution of each respective organ. Equivalent doses were calculated by OLINDA/EXM using the MIRD formalism. Tumor uptake was rapid from 0 to 1 h after injection for all 3 radioconjugates. Normal-tissue ratios as represented by tumor-to-liver, tumor-to-kidney, and tumor-to-muscle ratios increased significantly over time, with [Co]Co-DOTATATE reaching the highest ratio of all radioconjugates. For [Co]Co-DOTATATE, the tumor-to-liver ratio increased to 65 ± 16 at 4 h and 50 ± 6 at 24 h, which were 15 ( < 0.001) and 30 ( < 0.001) times higher, respectively, than the corresponding ratios for [Cu]Cu-DOTATATE and 5 ( < 0.001) times higher than that of [Ga]Ga-DOTATATE at 1 h. Correspondingly, tumor-to-kidney and tumor-to-muscle ratios for [Co]Co-DOTATATE were 4 ( < 0.001) and 11 ( < 0.001) times higher than that of [Cu]Cu-DOTATATE at 24 h. An equivalent dose was calculated as 9.6E-02 mSv/MBq for [Co]Co-DOTATATE. [Co]Co-DOTATATE demonstrated superior image contrast compared with [Cu]Cu-DOTATATE and [Ga]Ga-DOTATATE for PET imaging of somatostatin receptor-expressing tumors, warranting translation into clinical trials. Dosimetry calculations found that effective doses for [Co]Co-DOTATATE were comparable to those for both [Cu]Cu-DOTATATE and [Ga]Ga-DOTATATE.
在注射后晚期进行 PET 成像可能允许示踪剂从正常组织中清除，从而提高图像对比度和检测能力。60Co 是一种很有前途的同位素，具有较高的正电子产率和较长的半衰期，适合在延迟时间点成像。在这里，我们通过 PET/CT 成像比较了三种放射性缀合物[Ga]Ga-DOTATATE、[Cu]Cu-DOTATATE 和[Co]Co-DOTATATE 在表达生长抑素受体的 AR42J 皮下肿瘤的 NOD-SCID 小鼠中的情况。60Co 和 63Cu 是通过 Fe(d,n)60Co 和 Ni(p,n)63Cu 核反应产生的，而 67Ga 是从 Ge/Ga 发生器中获得的。通过在醋酸钠缓冲液和 4-(2-羟乙基)-1-哌嗪乙磺酸缓冲液中加热，分别将 DOTATATE 标记到 60Co 和 63Cu 上。在注射后 0-1 h 对 AR42J 肿瘤荷瘤小鼠进行动态扫描。对于 63Cu 和 60Co，还在 4 和 24 h 后进行了晚期成像。剂量计算基于已知的生物分布。通过对每个器官的生物分布进行拟合指数函数积分，计算每个器官的累积衰变数。使用 MIRD 形式主义，通过 OLINDA/EXM 计算等效剂量。在注射后 0-1 h 内，所有三种放射性缀合物在肿瘤中的摄取均迅速增加。代表肿瘤与肝脏、肿瘤与肾脏和肿瘤与肌肉的正常组织比随着时间的推移显著增加，其中[Co]Co-DOTATATE 达到了所有放射性缀合物中最高的比值。对于[Co]Co-DOTATATE，在 4 h 时肿瘤与肝脏的比值增加到 65 ± 16，在 24 h 时增加到 50 ± 6，分别是[Cu]Cu-DOTATATE 相应比值的 15 倍(<0.001)和 30 倍(<0.001)，在 1 h 时是[Ga]Ga-DOTATATE 的 5 倍(<0.001)。相应地，在 24 h 时，[Co]Co-DOTATATE 的肿瘤与肾脏和肿瘤与肌肉的比值分别是[Cu]Cu-DOTATATE 的 4 倍(<0.001)和 11 倍(<0.001)。计算出的[Co]Co-DOTATATE 的等效剂量为 9.6E-02 mSv/MBq。与[Cu]Cu-DOTATATE 和[Ga]Ga-DOTATATE 相比，[Co]Co-DOTATATE 对表达生长抑素受体的肿瘤的 PET 成像显示出更好的图像对比度，有必要将其转化为临床试验。剂量计算发现，[Co]Co-DOTATATE 的有效剂量与[Cu]Cu-DOTATATE 和[Ga]Ga-DOTATATE 相当。
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