Muylle Kristoff, Flamen Patrick, Vugts Danielle J, Guiot Thomas, Ghanem Ghanem, Meuleman Nathalie, Bourgeois Pierre, Vanderlinden Bruno, van Dongen Guus A M S, Everaert Hendrik, Vaes Mélanie, Bron Dominique
MIMA Research Group, Vrije Universiteit Brussel, Brussels, Belgium,
Eur J Nucl Med Mol Imaging. 2015 Jul;42(8):1304-14. doi: 10.1007/s00259-015-3025-6. Epub 2015 Mar 20.
To compare using immuno-PET/CT the distribution of (89)Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with (90)Y-labelled rituximab in CD20+ B-cell lymphoma.
Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline (89)Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m(2)) of unlabelled rituximab followed by injection of (89)Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by (90)Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed.
With a cold rituximab preload, the calculated whole-body dose of (90)Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59% and 87% was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion.
Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the "prerituximab era". Clinical Trial Application: CTA 2011-005474-38 TRIAL REGISTRY: EudraCT.
比较免疫正电子发射断层扫描/计算机断层扫描（immuno-PET/CT）在未使用未标记利妥昔单抗预负荷和使用未标记利妥昔单抗预负荷情况下，（89）Zr标记的利妥昔单抗的分布情况，以评估未标记利妥昔单抗预负荷对后续用（90）Y标记的利妥昔单抗进行放射免疫治疗在CD20 + B细胞淋巴瘤中的肿瘤靶向性和辐射剂量的影响。
前瞻性纳入5例患有CD20 + B细胞淋巴瘤且疾病进展的患者。所有患者均经历三个研究阶段：初始剂量测定阶段，进行无冷预负荷的基线（89）Zr - 利妥昔单抗PET/CT成像；3周后进行第二个剂量测定阶段，给予标准预负荷（250 mg/m²）的未标记利妥昔单抗，随后注射（89）Zr - 利妥昔单抗；1周后进行治疗阶段，给予未标记利妥昔单抗，随后给予（90）Y - 利妥昔单抗。评估PET/CT成像以及器官和病变对示踪剂的摄取情况。
在所有患者中，使用冷利妥昔单抗预负荷后，计算得出的（90）Y - 利妥昔单抗全身剂量相似（平均0.87 mSv/MBq，范围0.82 - 0.99 mSv/MBq）。在两名循环CD20 + B细胞保留的患者中，未进行预负荷时，全身剂量分别增加了59%和87%。这种辐射剂量的增加主要是由于未进行预负荷时脾脏接受的剂量高出12.4倍至15倍。在其他三名B细胞耗竭的患者中，未观察到全身剂量有显著变化。未进行预负荷时，B细胞耗竭的患者中肿瘤摄取始终较高。
对于大多数适合放射免疫治疗的患者，即先前接受过含利妥昔单抗治疗方案治疗的患者，给予标准预负荷的未标记利妥昔单抗会损害放射性缀合物对肿瘤的靶向性。这种常见做法可能需要重新考虑并进一步评估，因为这种高预负荷的理论依据源于“利妥昔单抗前时代”。临床试验应用：CTA 2011 - 005474 - 38试验注册：EudraCT
