Van Binnebeek Sofie, Baete Kristof, Vanbilloen Bert, Terwinghe Christelle, Koole Michel, Mottaghy Felix M, Clement Paul M, Mortelmans Luc, Haustermans Karin, Van Cutsem Eric, Verbruggen Alfons, Bogaerts Kris, Verslype Chris, Deroose Christophe M
Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium,
Eur J Nucl Med Mol Imaging. 2014 Jun;41(6):1141-57. doi: 10.1007/s00259-013-2670-x. Epub 2014 Mar 26.
Assessment of kidney function evolution after (90)Y-DOTATOC peptide receptor radionuclide therapy (PRRT) with capped activity administration based on a 37-Gy threshold of biological effective dose (BED) to the kidney.
In a prospective phase II study, patients with metastasized neuroendocrine tumours were evaluated for therapy using 185 MBq (111)In-pentetreotide with amino acid coinfusion. Planar whole-body images were acquired at four time-points after injection and kidney volumes were measured using CT/MRI. BED to the kidneys was estimated using an extended BED formula and biexponential renal clearance. Based on published BED dose-toxicity relationships, we allowed a maximal kidney BED of 37 Gy; if the calculated BED exceeded 37 Gy, treatment activity was reduced accordingly. Kidney function was assessed at baseline and at 18 months, predominantly using (51)Cr-EDTA. The rate of renal function decline was expressed as annual glomerular filtration rate loss (aGFRL).
Only 22 of 50 patients reached the 18-months time-point, with most missing patients having died due to disease progression. In the 22 patients who reached 18 months, no rapid kidney function deterioration was observed over the 18 months, aGFRL >33% was not seen, and only three patients showed an increase of one toxicity grade and one patient an increase of two grades. No significant correlations between kidney volume (p = 0.35), baseline GFR (p = 0.18), risk factors for renal function loss (p = 0.74) and aGFRL were observed. Among the 28 patients who did not reach 18 months, one developed grade 4 kidney toxicity at 15 months after PRRT.
Prospective dosimetry using a 37 Gy BED as the threshold for kidney toxicity is a good guide for (90)Y-DOTATOC PRRT and is associated with a low risk of rapid renal function deterioration and evolution to severe nephrotoxicity.
基于肾脏生物有效剂量（BED）37 Gy阈值，评估给予限定活度的（90）Y- DOTATOC肽受体放射性核素治疗（PRRT）后肾功能的变化。
在一项前瞻性II期研究中，对转移性神经内分泌肿瘤患者使用185 MBq（111）In- 喷替肽并联合输注氨基酸进行治疗评估。注射后在四个时间点采集全身平面图像，并使用CT/MRI测量肾脏体积。使用扩展的BED公式和双指数肾脏清除率估算肾脏的BED。根据已发表的BED剂量-毒性关系，我们设定肾脏的最大BED为37 Gy；如果计算出的BED超过37 Gy，则相应降低治疗活度。主要使用（51）Cr- 乙二胺四乙酸在基线和18个月时评估肾功能。肾功能下降率以每年肾小球滤过率损失（aGFRL）表示。
50例患者中只有22例达到18个月时间点，大多数未达该时间点的患者因疾病进展死亡。在达到18个月的22例患者中，在18个月期间未观察到肾功能快速恶化，未出现aGFRL>33%的情况，只有3例患者毒性等级增加1级，1例患者毒性等级增加2级。未观察到肾脏体积（p = 0.35）、基线肾小球滤过率（p = 0.18）、肾功能丧失危险因素（p = 0.74）与aGFRL之间存在显著相关性。在未达到18个月的28例患者中，1例在PRRT后15个月出现4级肾脏毒性。
以前瞻性剂量测定法将37 Gy BED作为肾脏毒性阈值，对（90）Y- DOTATOC PRRT是一个很好的指导，并且与肾功能快速恶化和发展为严重肾毒性的低风险相关。
