Radiopharmaceuticals as Novel Immune System Tracers

Ridge, Natalie A.; Rajkumar-Calkins, Anne; Dudzinski, Stephanie O.; Kirschner, Austin N.; Newman, N.B.

doi:10.1016/j.adro.2022.100936

Cited by 2 publications

(2 citation statements)

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“…89 Zr-iPET plays a crucial role in immunotherapy because of its innate characteristics, such as a physical half-life of 78.41 h and a β + decay of 23%, which make it a suitable tracer for the imaging of antibodies and the precise evaluation of drug pharmacokinetics and biodistribution in vivo [35,[39][40][41][42]. Recently, several PD-L1/PD-1 ICI mAb-based 89 Zr-iPET tracers have been investigated in clinical trials [43][44][45][46][47][48][49] and reviewed in relevant studies [41,50].…”

Section: Introductionmentioning

confidence: 99%

“…pharmacokinetics and biodistribution in vivo [35,[39][40][41][42]. Recently, several PD-L1/PD-1 ICI mAb-based 89 Zr-iPET tracers have been investigated in clinical trials [43][44][45][46][47][48][49] and reviewed in relevant studies [41,50]. The initial step in the preparation of 89 Zr-iPET tracers involves the development of an immunoconjugate.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Chelator-to-Antibody Ratio on Development of 89Zr-iPET Tracer for Imaging of PD-L1 Expression on Tumor

Tsai,

Farn,

et al. 2023

IJMS

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89Zr-iPET has been widely used for preclinical and clinical immunotherapy studies to predict patient stratification or evaluate therapeutic efficacy. In this study, we prepared and evaluated 89Zr-DFO-anti-PD-L1-mAb tracers with varying chelator-to-antibody ratios (CARs), including 89Zr-DFO-anti-PD-L1-mAb_3X (tracer_3X), 89Zr-DFO-anti-PD-L1-mAb_10X (tracer_10X), and 89Zr-DFO-anti-PD-L1-mAb_20X (tracer_20X). The DFO-anti-PD-L1-mAb conjugates with varying CARs were prepared using a random conjugation method and then subjected to quality control. The conjugates were radiolabeled with 89Zr and evaluated in a PD-L1-expressing CT26 tumor-bearing mouse model. Next, iPET imaging, biodistribution, pharmacokinetics, and ex vivo pathological and immunohistochemical examinations were conducted. LC–MS analysis revealed that DFO-anti-PD-L1-mAb conjugates were prepared with CARs ranging from 0.4 to 2.0. Radiochemical purity for all tracer groups was >99% after purification. The specific activity levels of tracer_3X, tracer_10X, and tracer_20X were 2.2 ± 0.6, 8.2 ± 0.6, and 10.5 ± 1.6 μCi/μg, respectively. 89Zr-iPET imaging showed evident tumor uptake in all tracer groups and reached the maximum uptake value at 24 h postinjection (p.i.). Biodistribution data at 168 h p.i. revealed that the tumor-to-liver, tumor-to-muscle, and tumor-to-blood uptake ratios for tracer_3X, tracer_10X, and tracer_20X were 0.46 ± 0.14, 0.58 ± 0.33, and 1.54 ± 0.51; 4.7 ± 1.3, 7.1 ± 3.9, and 14.7 ± 1.1; and 13.1 ± 5.8, 19.4 ± 13.8, and 41.3 ± 10.6, respectively. Significant differences were observed between tracer_3X and tracer_20X in the aforementioned uptake ratios at 168 h p.i. The mean residence time and elimination half-life for tracer_3X, tracer_10X, and tracer_20X were 25.4 ± 4.9, 24.2 ± 6.1, and 25.8 ± 3.3 h and 11.8 ± 0.5, 11.1 ± 0.7, and 11.7 ± 0.6 h, respectively. No statistical differences were found between-tracer in the aforementioned pharmacokinetic parameters. In conclusion, 89Zr-DFO-anti-PD-L1-mAb tracers with a CAR of 1.4–2.0 may be better at imaging PD-L1 expression in tumors than are traditional low-CAR 89Zr-iPET tracers.

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