Crump Institute for Molecular Imaging, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, California.
J Nucl Med. 2014 Mar;55(3):452-9. doi: 10.2967/jnumed.113.120873. Epub 2014 Feb 6.
Prostate stem cell antigen (PSCA) is expressed on the cell surface in 83%-100% of local prostate cancers and 87%-100% of prostate cancer bone metastases. In this study, we sought to develop immunoPET agents using (124)I- and (89)Zr-labeled anti-PSCA A11 minibodies (scFv-CH3 dimer, 80 kDa) and evaluate their use for quantitative immunoPET imaging of prostate cancer.
A11 anti-PSCA minibody was alternatively labeled with (124)I- or (89)Zr-desferrioxamine and injected into mice bearing either matched 22Rv1 and 22Rv1×PSCA or LAPC-9 xenografts. Small-animal PET data were obtained and quantitated with and without recovery coefficient-based partial-volume correction, and the results were compared with ex vivo biodistribution.
Rapid and specific localization to PSCA-positive tumors and high-contrast imaging were observed with both (124)I- and (89)Zr-labeled A11 anti-PSCA minibody. However, the differences in tumor uptake and background uptake of the radiotracers resulted in different levels of imaging contrast. The nonresidualizing (124)I-labeled minibody had lower tumor uptake (3.62 ± 1.18 percentage injected dose per gram [%ID/g] 22Rv1×PSCA, 3.63 ± 0.59 %ID/g LAPC-9) than the residualizing (89)Zr-labeled minibody (7.87 ± 0.52 %ID/g 22Rv1×PSCA, 9.33 ± 0.87 %ID/g LAPC-9, P < 0.0001 for each), but the (124)I-labeled minibody achieved higher imaging contrast because of lower nonspecific uptake and better tumor-to-soft-tissue ratios (22Rv1×PSCA:22Rv1 positive-to-negative tumor, 13.31 ± 5.59 (124)I-A11 and 4.87 ± 0.52 (89)Zr-A11, P = 0.02). Partial-volume correction was found to greatly improve the correspondence between small-animal PET and ex vivo quantification of tumor uptake for immunoPET imaging with both radionuclides.
Both (124)I- and (89)Zr-labeled A11 anti-PSCA minibody showed high-contrast imaging of PSCA expression in vivo. However, the (124)I-labeled A11 minibody was found to be the superior imaging agent because of lower nonspecific uptake and higher tumor-to-soft-tissue contrast. Partial-volume correction was found to be essential for robust quantification of immunoPET imaging with both (124)I- and (89)Zr-labeled A11 minibody.
前列腺干细胞抗原（PSCA）在 83%-100%局部前列腺癌和 87%-100%前列腺癌骨转移中表达于细胞表面。本研究旨在开发使用（124）I-和（89）Zr 标记的抗 PSCA A11 小抗体（scFv-CH3 二聚体，80 kDa）的免疫 PET 试剂，并评估其用于前列腺癌定量免疫 PET 成像的用途。
A11 抗 PSCA 小抗体分别用（124）I-或（89）Zr-去铁胺标记，并注入携带匹配的 22Rv1 和 22Rv1×PSCA 或 LAPC-9 异种移植物的小鼠体内。获得小动物 PET 数据，并使用和不使用基于恢复系数的部分体积校正进行定量，并将结果与体外生物分布进行比较。
用（124）I-和（89）Zr 标记的 A11 抗 PSCA 小抗体均观察到快速和特异性定位到 PSCA 阳性肿瘤和高对比度成像。然而，放射性示踪剂的肿瘤摄取和背景摄取差异导致成像对比度不同。非残留（124）I 标记的小抗体的肿瘤摄取率较低（22Rv1×PSCA 为 3.62±1.18%注入剂量/克[％ID/g]，LAPC-9 为 3.63±0.59％ID/g）比残留（89）Zr 标记的小抗体（22Rv1×PSCA 为 7.87±0.52％ID/g，LAPC-9 为 9.33±0.87％ID/g，P<0.0001），但（124）I 标记的小抗体由于较低的非特异性摄取和更好的肿瘤与软组织比值（22Rv1×PSCA：22Rv1 阳性与阴性肿瘤，13.31±5.59（124）I-A11 和 4.87±0.52（89）Zr-A11，P=0.02），实现了更高的成像对比度。发现部分体积校正对于使用两种放射性核素进行免疫 PET 成像的小动物 PET 与体外定量之间的对应关系非常重要。
（124）I-和（89）Zr 标记的 A11 抗 PSCA 小抗体均在体内显示出 PSCA 表达的高对比度成像。然而，（124）I 标记的 A11 小抗体由于较低的非特异性摄取和较高的肿瘤与软组织对比度，被发现是更好的成像试剂。发现部分体积校正对于使用（124）I-和（89）Zr 标记的 A11 小抗体进行稳健的免疫 PET 成像定量至关重要。
