Journal article
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, Vol.9(1), 79
11/26/2024
DOI: 10.1186/s41181-024-00313-8
PMCID: PMC11599518
PMID: 39589608
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.
Details
- Title: Subtitle
- SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203Pb-PSC-panitumumab in NRG mice
- Creators
- Nasim Sarrami - University of AlbertaBryce Nelson - University of AlbertaSamantha Leier - University of AlbertaJohn Wilson - University of AlbertaConrad Chan - University of TorontoJalna Meens - Princess Margaret Cancer CentreTeesha Komal - University Health NetworkLaurie Ailles - Princess Margaret Cancer CentreMelinda Wuest - University of AlbertaMichael Schultz - Viewpoint Molecular TargetingAfsaneh Lavasanifar - University of AlbertaRaymond M. Reilly - Princess Margaret Cancer CentreFrank Wuest - University of Alberta
- Resource Type
- Journal article
- Publication Details
- EJNMMI radiopharmacy and chemistry, Vol.9(1), 79
- DOI
- 10.1186/s41181-024-00313-8
- PMID
- 39589608
- PMCID
- PMC11599518
- NLM abbreviation
- EJNMMI Radiopharm Chem
- ISSN
- 2365-421X
- eISSN
- 2365-421X
- Publisher
- Springer International Publishing
- Grant note
- NSERC-CREATE "Polymer Nanoparticles for Drug Delivery (PoND)" programAlberta Innovates, and Graduate scholarships from the Faculty of Pharmacy and Pharmaceutical Sciences of the University of Alberta
Nasim Sarrami expresses gratitude for the NSERC-CREATE "Polymer Nanoparticles for Drug Delivery (PoND)" program, Alberta Innovates, and Graduate scholarships from the Faculty of Pharmacy and Pharmaceutical Sciences of the University of Alberta. The authors thank the Cross Cancer Institute pharmacy for generously gifting Vectibex (R).
- Language
- English
- Date published
- 11/26/2024
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984752658502771
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