SPECT/CT imaging of EGFR-positive head and neck squamous cell carcinoma patient-derived xenografts with 203 Pb-PSC-panitumumab in NRG mice.

Background: The objective of this research was the development and evaluation of ²⁰³ Pb-labelled panitumumab ( ²⁰³ Pb-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 ²⁰³ Pb offer an excellent opportunity for developing immuno-SPECT radioligands. Moreover, ²⁰³ Pb has a complementary therapeutic radionuclide ( ²¹² Pb), making ²⁰³ Pb and ²¹² Pb 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 [ ²⁰³ Pb]Pb(OAc) ₂ , and the incorporation efficiency was determined using radio-TLC. ²⁰³ Pb-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 ²⁰³ Pb-panitumumab injection. The tumour and normal tissues were collected and weighed, and uptake of ²⁰³ Pb 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 ²⁰³ Pb-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 ²⁰³ Pb-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 ²⁰³ Pb-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 ²⁰³ Pb-PSC-panitumumab uptake.
Conclusions: Panitumumab was successfully and reproducibly labelled with ²⁰³ Pb in high radiochemical purity using the chelator PSC-NCS. ²⁰³ Pb-PSC-panitumumab was specifically accumulated and retained in EGFR + tumours in NRG mice with s.c. HNSCC PDX. ²⁰³ Pb-PSC-panitumumab is a suitable immuno-SPECT radioligand for imaging EGFR + tumours and has great potential for combining with ²¹² Pb-PSC-panitumumab in a radiotheranostic strategy for imaging and treating HNSCC.
Competing Interests: Declarations. Ethics approval and consent to participate: All experimental protocols were approved by the Research Ethics Board at the University Health Network (Protocol No. 12–5639). All methods were performed per the ethical standards laid down in the Declaration of Helsinki and its later amendments or comparable ethical standards. Consent for publication: Not applicable. Competing interests: All authors declare no competing financial or non-financial interests.
(© 2024. The Author(s).)