Jackson Price, Hofman Michael, McIntosh Lachlan, Buteau James Patrick, Ravi Kumar Aravind
Molecular Imaging and Therapeutic Nuclear Medicine, Dept of Cancer Imaging, The Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Dept of Oncology, The University of Melbourne, Melbourne, Australia.
Molecular Imaging and Therapeutic Nuclear Medicine, Dept of Cancer Imaging, The Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Dept of Oncology, The University of Melbourne, Melbourne, Australia.
Semin Nucl Med. 2022 Mar;52(2):243-254. doi: 10.1053/j.semnuclmed.2021.11.003. Epub 2021 Dec 8.
Radionuclide therapy using the small molecule PSMA bound to the beta-emitting radionuclide, Lutetium-177 (Lu-PSMA) has demonstrated efficacy and survival benefit castrate resistant metastatic disease and represents a novel new line of therapy. Whilst dosimetry was critical for early development, it was not incorporated into either the TheraP or VISION randomized studies, highlighting the difficulty of adopting dosimetry in routine clinical practice. Accumulated clinical experience has also shown that the common (and generally low grade) toxicities such as nausea, xerostomia, and cytopenias are not readily predicted on the basis of dosimetry estimates. The majority of dosimetry and clinical literature deals with the radiopharmaceutical Lu-PSMA-617 which displays relatively consistent patterns of retention among normal tissues and high specificity for metastatic prostate cancer phenotypes. Population dosimetry incorporating estimates to the kidneys, salivary glands, and bone marrow have been widely reported the typical range of doses is becoming well established. There is growing interest on tumor dosimetry in Lu-PSMA-617 therapy as an overall modest side-effect profile from primary organ retention has been observed. A focus away from normal organ dosimetry to whole body tumor dosimetry may enable early prediction of treatment failure. Given the safety of Lu-PSMA there is also potential to escalate administered radioactivity to further improve outcomes. Importantly, the variability of uptake between individuals, both to tumor and normal organs, has also been highlighted which provides some rationale for the utility of personalized radiation analysis to optimize treatment based on potential toxicity thresholds or tumor control. Methods to perform dosimetry using serial post treatment imaging may incorporate planar, 3D SPECT, or hybrid datasets. Reliable measurements may be obtained through either method, however, continued developments in computational analysis are better suited to fully 3D imaging; particularly in conjunction with volumetric CT to assist with alignment and contouring. Dose analysis over sequential treatment cycles is vital to understand the radiobiology of these treatments which is unique compared to external beam therapy due to dose rate, fractionation scheme, and potential for intratumoral nonuniformity.
使用与发射β射线的放射性核素镥-177（Lu-PSMA）结合的小分子PSMA进行放射性核素治疗，已证明对去势抵抗性转移性疾病有效并能带来生存获益，代表了一种新的治疗方法。虽然剂量测定对早期研发至关重要，但它未被纳入TheraP或VISION随机研究中，这凸显了在常规临床实践中采用剂量测定的困难。积累的临床经验还表明，诸如恶心、口干和血细胞减少等常见（且通常为低级别）毒性，难以根据剂量测定估计轻易预测。大多数剂量测定和临床文献涉及放射性药物Lu-PSMA-617，其在正常组织中的滞留模式相对一致，对转移性前列腺癌表型具有高特异性。纳入对肾脏、唾液腺和骨髓估计的群体剂量测定已被广泛报道，典型的剂量范围已逐渐明确。由于观察到原发性器官滞留导致的总体副作用较小，人们对Lu-PSMA-617治疗中的肿瘤剂量测定越来越感兴趣。从关注正常器官剂量测定转向全身肿瘤剂量测定，可能有助于早期预测治疗失败。鉴于Lu-PSMA的安全性，也有可能提高给药放射性以进一步改善疗效。重要的是，个体之间肿瘤和正常器官摄取的变异性也已得到强调，这为基于潜在毒性阈值或肿瘤控制进行个性化放射分析以优化治疗提供了一些依据。使用治疗后系列影像进行剂量测定的方法可包括平面、三维单光子发射计算机断层扫描（3D SPECT）或混合数据集。通过这两种方法都可获得可靠测量结果，然而，计算分析的持续发展更适合全三维成像；特别是与容积CT结合以辅助对齐和勾勒轮廓。连续治疗周期的剂量分析对于理解这些治疗的放射生物学至关重要，由于剂量率、分割方案以及肿瘤内不均匀性的可能性，这些治疗的放射生物学与外照射疗法相比具有独特性。
