SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice
Abstract Background The objective of this research was the development and evaluation of 203Pb-labelled panitumumab (203Pb-PSC-panitumumab) as an immuno-SPECT radioligand for the detection of EGFR + head and neck squamous cell carcinoma (HNSCC) in a patient-derived xenograft (PDX) mouse model. The 5...
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2024-11-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
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| Online Access: | https://doi.org/10.1186/s41181-024-00313-8 |
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| author | Nasim Sarrami Bryce Nelson Samantha Leier John Wilson Conrad Chan Jalna Meens Teesha Komal Laurie Ailles Melinda Wuest Michael Schultz Afsaneh Lavasanifar Raymond M. Reilly Frank Wuest |
| author_facet | Nasim Sarrami Bryce Nelson Samantha Leier John Wilson Conrad Chan Jalna Meens Teesha Komal Laurie Ailles Melinda Wuest Michael Schultz Afsaneh Lavasanifar Raymond M. Reilly Frank Wuest |
| author_sort | Nasim Sarrami |
| collection | DOAJ |
| description | Abstract Background The objective of this research was the development and evaluation of 203Pb-labelled panitumumab (203Pb-PSC-panitumumab) as an immuno-SPECT radioligand for the detection of EGFR + head and neck squamous cell carcinoma (HNSCC) in a patient-derived xenograft (PDX) mouse model. The 51.9 h physical half-life and favourable γ-emission (279 keV; 81%) of 203Pb offer an excellent opportunity for developing immuno-SPECT radioligands. Moreover, 203Pb has a complementary therapeutic radionuclide (212Pb), making 203Pb and 212Pb an ideal matched radiotheranostic pair. Results Radiolabeling of panitumumab was performed at a pH of 5.0 and room temperature for 5–10 min with [203Pb]Pb(OAc)2, and the incorporation efficiency was determined using radio-TLC. 203Pb-PSC-panitumumab (~ 10 MBq, 140 μl of saline) was injected into the tail vein of NRG mice bearing subcutaneous (s.c.) HNSCC patient-derived xenografts (PDX). SPECT/CT images were acquired at 48 and 120 h post-injection. For biodistribution studies, mice were euthanized five days after 203Pb-panitumumab injection. The tumour and normal tissues were collected and weighed, and uptake of 203Pb was measured in a γ-counter. The uptake was calculated as the percent injected dose per gram of each tissue (ID%/g). Blocking experiments were performed by pretreating a group of mice (n = 5) with 1 mg of panitumumab 1 h before administering 203Pb-PSC-panitumumab. 4–5 chelators of a new lead-specific chelator (PSC) were attached per antibody; radiolabeling efficiency was 99.2 ± 0.7%. The isolated radiochemical yield of 203Pb-PSC-panitumumab was 41.4 ± 8% (n = 5), and the molar activity was 1.2 ± 0.35 GB/mg. SPECT imaging and biodistribution confirmed high accumulation and retention of 203Pb-PSC-panitumumab in the tumour (26% ID/g) at 120 h post-injection (p.i.), which could be reduced to 6.2%ID/g at 120 h p.i. by predosing with panitumumab (1 mg) confirming EGFR specificity of 203Pb-PSC-panitumumab uptake. Conclusions Panitumumab was successfully and reproducibly labelled with 203Pb in high radiochemical purity using the chelator PSC-NCS. 203Pb-PSC-panitumumab was specifically accumulated and retained in EGFR + tumours in NRG mice with s.c. HNSCC PDX. 203Pb-PSC-panitumumab is a suitable immuno-SPECT radioligand for imaging EGFR + tumours and has great potential for combining with 212Pb-PSC-panitumumab in a radiotheranostic strategy for imaging and treating HNSCC. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2024-11-01 |
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| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj-art-dbec871ee73f42fbb3a3914c8584d87c2024-12-01T12:51:12ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2024-11-019111310.1186/s41181-024-00313-8SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG miceNasim Sarrami0Bryce Nelson1Samantha Leier2John Wilson3Conrad Chan4Jalna Meens5Teesha Komal6Laurie Ailles7Melinda Wuest8Michael Schultz9Afsaneh Lavasanifar10Raymond M. Reilly11Frank Wuest12Faculty of Pharmacy and Pharmaceutical Sciences, University of AlbertaDepartment of Oncology, Cross Cancer Institute, University of AlbertaDepartment of Oncology, Cross Cancer Institute, University of AlbertaDepartment of Oncology, Cross Cancer Institute, University of AlbertaLeslie Dan Faculty of Pharmacy and Department of Pharmaceutical Sciences, University of TorontoPrincess Margaret Cancer CentreSTTARR Innovation Centre, University Health NetworkPrincess Margaret Cancer CentreDepartment of Oncology, Cross Cancer Institute, University of AlbertaViewpoint Molecular Targeting, IncFaculty of Pharmacy and Pharmaceutical Sciences, University of AlbertaLeslie Dan Faculty of Pharmacy and Department of Pharmaceutical Sciences, University of TorontoFaculty of Pharmacy and Pharmaceutical Sciences, University of AlbertaAbstract Background The objective of this research was the development and evaluation of 203Pb-labelled panitumumab (203Pb-PSC-panitumumab) as an immuno-SPECT radioligand for the detection of EGFR + head and neck squamous cell carcinoma (HNSCC) in a patient-derived xenograft (PDX) mouse model. The 51.9 h physical half-life and favourable γ-emission (279 keV; 81%) of 203Pb offer an excellent opportunity for developing immuno-SPECT radioligands. Moreover, 203Pb has a complementary therapeutic radionuclide (212Pb), making 203Pb and 212Pb an ideal matched radiotheranostic pair. Results Radiolabeling of panitumumab was performed at a pH of 5.0 and room temperature for 5–10 min with [203Pb]Pb(OAc)2, and the incorporation efficiency was determined using radio-TLC. 203Pb-PSC-panitumumab (~ 10 MBq, 140 μl of saline) was injected into the tail vein of NRG mice bearing subcutaneous (s.c.) HNSCC patient-derived xenografts (PDX). SPECT/CT images were acquired at 48 and 120 h post-injection. For biodistribution studies, mice were euthanized five days after 203Pb-panitumumab injection. The tumour and normal tissues were collected and weighed, and uptake of 203Pb was measured in a γ-counter. The uptake was calculated as the percent injected dose per gram of each tissue (ID%/g). Blocking experiments were performed by pretreating a group of mice (n = 5) with 1 mg of panitumumab 1 h before administering 203Pb-PSC-panitumumab. 4–5 chelators of a new lead-specific chelator (PSC) were attached per antibody; radiolabeling efficiency was 99.2 ± 0.7%. The isolated radiochemical yield of 203Pb-PSC-panitumumab was 41.4 ± 8% (n = 5), and the molar activity was 1.2 ± 0.35 GB/mg. SPECT imaging and biodistribution confirmed high accumulation and retention of 203Pb-PSC-panitumumab in the tumour (26% ID/g) at 120 h post-injection (p.i.), which could be reduced to 6.2%ID/g at 120 h p.i. by predosing with panitumumab (1 mg) confirming EGFR specificity of 203Pb-PSC-panitumumab uptake. Conclusions Panitumumab was successfully and reproducibly labelled with 203Pb in high radiochemical purity using the chelator PSC-NCS. 203Pb-PSC-panitumumab was specifically accumulated and retained in EGFR + tumours in NRG mice with s.c. HNSCC PDX. 203Pb-PSC-panitumumab is a suitable immuno-SPECT radioligand for imaging EGFR + tumours and has great potential for combining with 212Pb-PSC-panitumumab in a radiotheranostic strategy for imaging and treating HNSCC.https://doi.org/10.1186/s41181-024-00313-8PanitumumabPb-203Single-Photon Emission Computed Tomography (SPECT)Epidermal growth factor receptor (EGFR)RadiotheranosticsPb-212 |
| spellingShingle | Nasim Sarrami Bryce Nelson Samantha Leier John Wilson Conrad Chan Jalna Meens Teesha Komal Laurie Ailles Melinda Wuest Michael Schultz Afsaneh Lavasanifar Raymond M. Reilly Frank Wuest SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice EJNMMI Radiopharmacy and Chemistry Panitumumab Pb-203 Single-Photon Emission Computed Tomography (SPECT) Epidermal growth factor receptor (EGFR) Radiotheranostics Pb-212 |
| title | SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice |
| title_full | SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice |
| title_fullStr | SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice |
| title_full_unstemmed | SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice |
| title_short | SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice |
| title_sort | spect ct imaging of egfr positive head and neck squamous cell carcinoma patient derived xenografts with 203pb psc panitumumab in nrg mice |
| topic | Panitumumab Pb-203 Single-Photon Emission Computed Tomography (SPECT) Epidermal growth factor receptor (EGFR) Radiotheranostics Pb-212 |
| url | https://doi.org/10.1186/s41181-024-00313-8 |
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