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基于图像的 [Ac]Ac-PSMA-I&T 治疗剂量学及其子体特异性药代动力学的影响。

Image-based dosimetry for [Ac]Ac-PSMA-I&T therapy and the effect of daughter-specific pharmacokinetics.

机构信息

Department of Nuclear Medicine, LMU University Hospital, LMU Munich, Marchioninstrasse 15, 81377, Munich, Germany.

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.

出版信息

Eur J Nucl Med Mol Imaging. 2024 Jul;51(8):2504-2514. doi: 10.1007/s00259-024-06681-2. Epub 2024 Mar 21.

Abstract

PURPOSE

Although Fr and Bi have sufficient gamma emission probabilities, quantitative SPECT after [Ac]Ac-PSMA-I&T therapy remains challenging due to low therapeutic activities. Furthermore, Fr and Bi may underlie a different pharmacokinetics due to alpha recoil. We conducted a quantitative SPECT study and a urine analysis to investigate the pharmacokinetics of Fr and Bi and the impact on image-based lesion and kidney dosimetry.

METHODS

Five patients (7.7 ± 0.2 MBq [Ac]Ac-PSMA-I&T) underwent an abdominal SPECT/CT (1 h) at 24 and 48 h (Siemens Symbia T2, high-energy collimator, 440 keV/218 keV (width 20%), 78 keV (width 50%)). Quantitative SPECT was reconstructed using MAP-EM with attenuation and transmission-dependent scatter corrections and resolution modelling. Time-activity curves for kidneys (CT-based) and lesions (80% isocontour 24 h) were fitted mono-exponentially. Urine samples collected along with each SPECT/CT were measured in a gamma counter until secular equilibrium was reached.

RESULTS

Mean kidney and lesion effective half-lives were as follows: Bi, 27 ± 6/38 ± 10 h; Fr, 24 ± 6/38 ± 11 h; 78 keV, 23 ± 7/39 ± 13 h. The Bi-to-Fr kidney SUV ratio increased by an average of 9% from 24 to 48 h. Urine analysis revealed an increasing Bi-to-Ac ratio (24 h, 0.98 ± 0.15; 48 h, 1.08 ± 0.09). Mean kidney and lesion absorbed doses were 0.17 ± 0.06 and 0.36 ± 0.1 /MBq using Fr and Bi SPECT images, compared to 0.16 ± 0.05/0.18 ± 0.06 and 0.36 ± 0.1/0.38 ± 0.1 /MBq considering either the Fr or Bi SPECT.

CONCLUSION

SPECT/CT imaging and urine analysis showed minor differences of up to 10% in the daughter-specific pharmacokinetics. These variances had a minimal impact on the lesion and kidney dosimetry which remained within 8%.

摘要

目的

尽管镄(Fr)和铋(Bi)具有足够的伽马射线发射概率,但由于治疗活性低,[Ac]Ac-PSMA-I&T 治疗后的定量单光子发射计算机断层扫描(SPECT)仍然具有挑战性。此外,由于阿尔法反冲,Fr 和 Bi 可能具有不同的药代动力学。我们进行了一项定量 SPECT 研究和尿液分析,以研究 Fr 和 Bi 的药代动力学及其对基于图像的病变和肾脏剂量学的影响。

方法

5 名患者(7.7±0.2 MBq [Ac]Ac-PSMA-I&T)在 24 和 48 小时(西门子 Symbia T2,高能准直器,440keV/218keV(宽度 20%),78keV(宽度 50%))进行腹部 SPECT/CT(1 小时)。使用 MAP-EM 进行定量 SPECT 重建,包括衰减和传输相关散射校正以及分辨率建模。使用 80%等浓度 24 小时的病变(80%等浓度 24 小时)和肾脏(基于 CT)的时间-活性曲线进行单指数拟合。在达到放射性平衡之前,使用伽马计数器测量每次 SPECT/CT 时收集的尿液样本。

结果

肾脏和病变的有效半衰期平均值如下:Bi,27±6/38±10 小时;Fr,24±6/38±11 小时;78keV,23±7/39±13 小时。Bi 到 Fr 的肾脏 SUV 比值在 24 至 48 小时之间平均增加了 9%。尿液分析显示 Bi 到 Ac 的比值增加(24 小时,0.98±0.15;48 小时,1.08±0.09)。使用 Fr 和 Bi SPECT 图像,肾脏和病变的平均吸收剂量分别为 0.17±0.06 和 0.36±0.1 /MBq,而考虑 Fr 或 Bi SPECT 时,肾脏和病变的平均吸收剂量分别为 0.16±0.05/0.18±0.06 和 0.36±0.1/0.38±0.1 /MBq。

结论

SPECT/CT 成像和尿液分析显示,在子体特异性药代动力学方面,差异最小可达 10%。这些差异对病变和肾脏剂量学的影响最小,仍在 8%以内。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b8d/11178588/c5b0f31cca51/259_2024_6681_Fig1_HTML.jpg

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