用于荷瘤裸鼠体内90Y标记单克隆抗体初步探查的定量89Zr免疫正电子发射断层扫描

Quantitative 89Zr immuno-PET for in vivo scouting of 90Y-labeled monoclonal antibodies in xenograft-bearing nude mice.

作者信息

Verel Iris, Visser Gerard W M, Boellaard Ronald, Boerman Otto C, van Eerd Julliette, Snow Gordon B, Lammertsma Adriaan A, van Dongen Guus A M S

机构信息

Department of Otolaryngology/Head and Neck Surgery, VU University Medical Center, Amsterdam, The Netherlands.

出版信息

J Nucl Med. 2003 Oct;44(10):1663-70.

PMID:14530484

Abstract

UNLABELLED

Immuno-PET as a scouting procedure before radioimmunotherapy (RIT) aims at the confirmation of tumor targeting and the accurate estimation of radiation dose delivery to both tumor and normal tissues. Immuno-PET with (89)Zr-labeled monoclonal antibodies (mAbs) and (90)Y-mAb RIT might form such a valuable combination. In this study, the biodistribution of (89)Zr-labeled and (88)Y-labeled mAb ((88)Y as substitute for (90)Y) was compared and the quantitative imaging performance of (89)Zr immuno-PET was evaluated.

METHODS

Chimeric mAb (cmAb) U36, directed against an antigen preferentially expressed in head and neck cancer, was labeled with (89)Zr using the bifunctional chelate N-succinyldesferrioxamine B (N-sucDf) and with (88)Y using the bifunctional chelate p-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bz-DOTA). The radioimmunoconjugates were coinjected in xenograft-bearing nude mice, and biodistribution was determined at 3, 24, 48, 72, and 144 h after injection. (89)Zr was evaluated and compared with (18)F in phantom studies to determine linearity, resolution, and recovery coefficients, using a high-resolution research tomograph PET scanner. The potential of PET to quantify cmAb U36-N-sucDf-(89)Zr was evaluated by relating image-derived tumor uptake data (noninvasive method) to (89)Zr uptake data derived from excised tumors (invasive method).

RESULTS

(89)Zr-N-sucDf-labeled and (88)Y-p-SCN-Bz-DOTA-labeled cmAb U36 showed a highly similar biodistribution, except for sternum and thigh bone at later time points (72 and 144 h after injection). Small differences were found in kidney and liver. Imaging performance of (89)Zr approximates that of (18)F, whereas millimeter-sized (19-154 mg) tumors were visualized in xenograft-bearing mice after injection of cmAb U36-N-sucDf-(89)Zr. After correction for partial-volume effects, an excellent correlation was found between image-derived (89)Zr tumor radioactivity and gamma-counter (89)Zr values of excised tumors (R(2) = 0.79).

CONCLUSION

The similar biodistribution and the favorable imaging characteristics make (89)Zr a promising candidate for use as a positron-emitting surrogate for (90)Y.

摘要

未标记

免疫正电子发射断层扫描（Immuno-PET）作为放射免疫治疗（RIT）前的一种侦察程序，旨在确认肿瘤靶向性并准确估计肿瘤和正常组织的辐射剂量传递。用（89）Zr标记的单克隆抗体（mAb）进行免疫正电子发射断层扫描与（90）Y-mAb放射免疫治疗可能形成这样一种有价值的组合。在本研究中，比较了（89）Zr标记和（88）Y标记的mAb（（88）Y作为（90）Y的替代物）的生物分布，并评估了（89）Zr免疫正电子发射断层扫描的定量成像性能。

方法

针对头颈部癌中优先表达的一种抗原的嵌合mAb（cmAb）U36，使用双功能螯合剂N-琥珀酰去铁胺B（N-sucDf）用（89）Zr标记，使用双功能螯合剂对异硫氰酸苄基-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸（p-SCN-Bz-DOTA）用（88）Y标记。将放射性免疫缀合物共同注射到荷瘤裸鼠体内，并在注射后3、24、48、72和144小时测定生物分布。在体模研究中，使用高分辨率研究断层扫描正电子发射断层扫描仪对（89）Zr进行评估并与（18）F进行比较，以确定线性、分辨率和恢复系数。通过将图像衍生的肿瘤摄取数据（非侵入性方法）与切除肿瘤的（89）Zr摄取数据（侵入性方法）相关联，评估正电子发射断层扫描对cmAb U36-N-sucDf-（89）Zr进行定量的潜力。

结果

（89）Zr-N-sucDf标记和（88）Y-p-SCN-Bz-DOTA标记的cmAb U36显示出高度相似的生物分布，但在较晚时间点（注射后72和144小时）胸骨和大腿骨除外。在肾脏和肝脏中发现了微小差异。（89）Zr的成像性能接近（18）F，而在注射cmAb U36-N-sucDf-（89）Zr后，在荷瘤小鼠中可观察到毫米大小（19 - 154毫克）的肿瘤。在校正部分容积效应后，发现图像衍生的（89）Zr肿瘤放射性与切除肿瘤的γ计数器（89）Zr值之间具有良好的相关性（R（2） = 0.79）。