177Lu-DKFZ-PSMA-617治疗转移性去势抵抗性前列腺癌患者后的治疗剂量测定

Post-therapeutic dosimetry of 177Lu-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer.

作者信息

Yadav Madhav P, Ballal Sanjana, Tripathi Madhavi, Damle Nishikant A, Sahoo Ranjit K, Seth Amlesh, Bal Chandrasekhar

机构信息

Departments of aNuclear Medicine bMedical Oncology cUrology, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Nucl Med Commun. 2017 Jan;38(1):91-98. doi: 10.1097/MNM.0000000000000606.

DOI:10.1097/MNM.0000000000000606

PMID:27782913

Abstract

OBJECTIVE

Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients.

MATERIALS AND METHODS

After obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60 min before Lu-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.52±1.3 GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168 h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software.

RESULTS

A total of 26 mCRPC patients with a mean age of 66.30±9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24±0.26 and 0.99±0.31 mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36±0.10, 0.243±0.09 and 0.048±0.05 mGy/MBq, respectively. The mean whole-body dose was 0.016±0.003 mGy/MBq.

CONCLUSION

Lu-DKFZ-PSMA-617 therapy is a safe option in the treatment of mCRPC patients.

摘要

目的

基于尿素的化合物Lu-DKFZ-PSMA-617与前列腺特异性膜抗原的细胞外结构域结合，从而为转移性去势抵抗性前列腺癌（mCRPC）的治疗提供了一个有效的靶点。在其用于治疗之前，有必要研究这种放射性药物的辐射剂量测定，以确定可给予患者的安全活度，从而预防血液学、肾脏和肝脏毒性。因此，本研究旨在评估Lu-DKFZ-PSMA-617在CRPC患者中的药代动力学和剂量测定。

材料与方法

获得研究所伦理审查委员会的伦理许可后，我们招募了在Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT扫描中呈阳性的mCRPC患者。为保护肾脏，在输注Lu-DKFZ-PSMA-617前30至60分钟开始，输注在2升生理盐水中稀释的赖氨酸和精氨酸混合物。总体人群的平均给药活度为2.52±1.3 GBq。为进行剂量测定，每位患者分别在0.5、3.5、24、48、72、96、120、144和168小时进行9次全身平面扫描，并采集血液和尿液样本。进行SPECT/CT以得出唾液腺（腮腺和颌下腺）和肿瘤的体积。使用OLINDA/EXM 1.0软件进行剂量学评估。

结果

共招募了26例mCRPC患者，平均年龄为66.30±9.95岁（范围：38 - 81岁）。在所有患者的泪腺、唾液腺（腮腺和颌下腺）、肝脏、脾脏、肾脏、肠道和膀胱中均观察到正常的生理性摄取。吸收剂量最高的器官是唾液腺，其次是肾脏，分别接受1.24±0.26和0.99±0.31 mGy/MBq。肝脏、膀胱和红骨髓的平均吸收剂量分别为0.36±0.10、0.243±0.09和0.048±0.05 mGy/MBq。全身平均剂量为0.016±0.003 mGy/MBq。