3.8 Article

Dose predictions for [177Lu]Lu-DOTA-panitumumab F(ab′)2 in NRG mice with HNSCC patient-derived tumour xenografts based on [64Cu]Cu-DOTA-panitumumab F(ab′)2 - implications for a PET theranostic strategy

期刊

出版社

SPRINGERNATURE
DOI: 10.1186/s41181-021-00140-1

关键词

Panitumumab; Cu-64; Lu-177; Dosimetry; Theranostics; Head and neck squamous cell carcinoma (HNSCC)

资金

  1. Canadian Cancer Society
  2. Queen Elizabeth II Graduate Scholarship in Science and Technology (QEII-GSST) from the Province of Ontario
  3. Centre for Pharmaceutical Oncology (CPO) at the University of Toronto
  4. Strategic Training in Transdisciplinary Radiation Science for the twenty-first Century [STARS21]
  5. Terry Fox Foundation
  6. Second Reuben Wells Fellowship
  7. University College Alumni Scholarship from the University of Toronto

向作者/读者索取更多资源

The study assessed the feasibility of a theranostic strategy using [Cu-64]Cu-DOTA-panitumumab F(ab')(2) for imaging HNSCC tumors and predicting radiation doses from RIT with [Lu-177]Lu-DOTA-panitumumab F(ab')(2). Results showed promising potential for RIT in HNSCC treatment, highlighting the need for further research to confirm the findings.
Background Epidermal growth factor receptors (EGFR) are overexpressed on many head and neck squamous cell carcinoma (HNSCC). Radioimmunotherapy (RIT) with F(ab')(2) of the anti-EGFR monoclonal antibody panitumumab labeled with the beta-particle emitter, Lu-177 may be a promising treatment for HNSCC. Our aim was to assess the feasibility of a theranostic strategy that combines positron emission tomography (PET) with [Cu-64]Cu-DOTA-panitumumab F(ab')(2) to image HNSCC and predict the radiation equivalent doses to the tumour and normal organs from RIT with [Lu-177]Lu-DOTA-panitumumab F(ab')(2). Results Panitumumab F(ab')(2) were conjugated to DOTA and complexed to Cu-64 or Lu-177 in high radiochemical purity (95.6 +/- 2.1% and 96.7 +/- 3.5%, respectively) and exhibited high affinity EGFR binding (K-d = 2.9 +/- 0.7 x 10(- 9) mol/L). Biodistribution (BOD) studies at 6, 24 or 48 h post-injection (p.i.) of [Cu-64]Cu-DOTA-panitumumab F(ab')(2) (5.5-14.0 MBq; 50 mu g) or [Lu-177]Lu-DOTA-panitumumab F(ab')(2) (6.5 MBq; 50 mu g) in NRG mice with s.c. HNSCC patient-derived xenografts (PDX) overall showed no significant differences in tumour uptake but modest differences in normal organ uptake were noted at certain time points. Tumours were imaged by microPET/CT with [Cu-64]Cu-DOTA-panitumumab F(ab')(2) or microSPECT/CT with [Lu-177]Lu-DOTA-panitumumab F(ab')(2) but not with irrelevant [Lu-177]Lu-DOTA-trastuzumab F(ab')(2). Tumour uptake at 24 h p.i. of [Cu-64]Cu-DOTA-panitumumab F(ab')(2) [14.9 +/- 1.1% injected dose/gram (%ID/g) and [Lu-177]Lu-DOTA-panitumumab F(ab')(2) (18.0 +/- 0.4%ID/g) were significantly higher (P < 0.05) than [Lu-177]Lu-DOTA-trastuzumab F(ab')(2) (2.6 +/- 0.5%ID/g), demonstrating EGFR-mediated tumour uptake. There were no significant differences in the radiation equivalent doses in the tumour and most normal organs estimated for [Lu-177]Lu-DOTA-panitumumab F(ab')(2) based on the BOD of [Cu-64]Cu-DOTA-panitumumab F(ab')(2) compared to those estimated directly from the BOD of [Lu-177]Lu-DOTA-panitumumab F(ab')(2) except for the liver and whole body which were modestly underestimated by [Cu-64]Cu-DOTA-panitumumab F(ab')(2). Region-of-interest (ROI) analysis of microPET/CT images provided dose estimates for the tumour and liver that were not significantly different for the two radioimmunoconjugates. Human doses from administration of [Lu-177]Lu-DOTA-panitumumab F(ab')(2) predicted that a 2 cm diameter HNSCC tumour in a patient would receive 1.1-1.5 mSv/MBq and the whole body dose would be 0.15-0.22 mSv/MBq. Conclusion A PET theranostic strategy combining [Cu-64]Cu-DOTA-panitumumab F(ab')(2) to image HNSCC tumours and predict the equivalent radiation doses in the tumour and normal organs from RIT with [Lu-177]Lu-DOTA-panitumumab F(ab')(2) is feasible. RIT with [Lu-177]Lu-DOTA-panitumumab F(ab')(2) may be a promising approach to treatment of HNSCC due to frequent overexpression of EGFR.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

3.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据