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Published on: July 31, 2017
Immuno-PET quantitation of de2-7 epidermal growth factor receptor expression in glioma using 124I-IMP-R4-labeled
Fook T Lee1, Graeme J O'Keefe, Hui K Gan
1Ludwig Institute for Cancer Research, Heidelberg, Victoria, Australia.
Unlabelled:
Overexpression, activation, and mutations of the epidermal growth factor receptor (EGFR) are commonly found in solid tumors. The aim of this study was to develop a PET-based method for detecting the constitutively active mutant de2-7 EGFR, which is associated with disease progression and resistance to chemotherapy and radiotherapy in glioma.
Methods:
The chimeric antibody ch806, which selectively binds an epitope of the EGFR that is exposed only on overexpressed, mutant, or ligand-activated forms of the receptor, was conjugated to the radiohalogen (124)I via the residualizing ligand IMP-R4, and in vitro properties were characterized. In vivo biodistribution and small-animal PET studies were performed in BALB/c nude mice bearing U87MG.de2-7 glioma xenografts. Imaging results were correlated with measured tumor uptake of the radioconjugate.
Results:
(124)I-IMP-R4-ch806 had an immunoreactivity of 78.3% and was stable for 7 d when incubated in serum in vitro. The biodistribution analysis of (124)I-IMP-R4-ch806 demonstrated a maximal uptake of 30.95 +/- 6.01 percentage injected dose per gram (%ID/g) in U87MG.de2-7 xenografts at 48 h after injection, with prolonged tumor retention (6.07 +/- 0.80 %ID/g at 216 h after injection). The tumor-to-blood ratio increased from 0.44 at 4 h after injection to a maximum of 4.70 at 168 h after injection. PET of (124)I-IMP-R4-ch806 biodistribution was able to clearly detect the U87MG.de2-7 tumors at 24 h after injection and for at least 168 h after injection. Correlation between tumor PET image quantitation of (124)I-IMP-R4-ch806 and %ID/g determined from resected tissues (r = 0.9350) was excellent.
Conclusion:
These results show that immuno-PET with (124)I-IMP-R4-ch806 is feasible and allows noninvasive quantitation of de2-7 EGFR expression in vivo.
Insights
This study developed a novel PET imaging method using (124)I-IMP-R4-ch806 to detect mutant de2-7 EGFR in glioma. The technique successfully visualized tumors and quantified receptor expression noninvasively.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Epidermal growth factor receptor (EGFR) overexpression, activation, and mutations are prevalent in solid tumors.
- Mutant de2-7 EGFR is linked to glioma progression and treatment resistance.
- Developing targeted imaging for mutant EGFR is crucial for effective cancer therapy.
Purpose of the Study:
- To develop a Positron Emission Tomography (PET)-based imaging method for detecting the constitutively active mutant de2-7 EGFR.
- To assess the feasibility and efficacy of using a specific antibody-radioconjugate for noninvasive imaging of mutant EGFR in glioma.
Main Methods:
- Conjugation of the chimeric antibody ch806 to the radiohalogen (124)I via the IMP-R4 ligand.
- In vitro characterization of the radioconjugate's properties, including stability and immunoreactivity.
- In vivo biodistribution and small-animal PET studies in glioma xenograft models.
- Correlation of imaging results with ex vivo tumor uptake measurements.
Main Results:
- The radioconjugate (124)I-IMP-R4-ch806 exhibited high immunoreactivity (78.3%) and stability in vitro.
- Maximal tumor uptake in xenografts reached 30.95% injected dose per gram at 48 hours, with prolonged retention.
- PET imaging clearly detected U87MG.de2-7 glioma xenografts from 24 to 168 hours post-injection.
- Excellent correlation (r=0.9350) was observed between PET quantitation and ex vivo tumor uptake.
Conclusions:
- Immuno-PET using (124)I-IMP-R4-ch806 is a feasible method for detecting de2-7 EGFR.
- This approach allows for noninvasive quantitation of de2-7 EGFR expression in vivo.
- The developed method holds promise for improved glioma diagnosis and treatment monitoring.
