Improved non-invasive positron emission tomographic imaging of chemotherapy-induced tumor cell death using Zirconium-89-labeled APOMAB

• Published in: EJNMMI radiopharmacy and chemistry Vol. 5; no. 1; p. 27
• Main Authors: Liapis, Vasilios, Tieu, William, Rudd, Stacey E., Donnelly, Paul S., Wittwer, Nicole L., Brown, Michael P., Staudacher, Alexander H.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 17-11-2020; Springer Nature B.V; SpringerOpen
• Subjects: Antibodies; Apoptosis; Cell death; chDAB4; Chelating agents; Chemotherapy; Imaging; Iodine; Iodine-124; Lymphoma; Medicine; Medicine & Public Health; Molecular Medicine; Monoclonal antibodies; Nuclear Chemistry; Nuclear Medicine; PET imaging; Pharmacotherapy; Radiology; Research Article; Sjogren's syndrome; Tumor cells; Tumors; Zirconium-89; Zirconium-89; Iodine-124; Chemotherapy; PET imaging; chDAB4
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-020-00109-6

Purpose
The chimeric monoclonal antibody (mAb) chDAB4 (APOMAB®) targets the Lupus associated (La)/Sjögren Syndrome-B (SSB) antigen, which is over-expressed in tumors but only becomes available for antibody binding in dead tumor cells. Hence, chDAB4 may be used as a novel theranostic tool to distinguish between responders and nonresponders early after chemotherapy. Here, we aimed to ascertain which positron emitter, Zirconium-89 ([
89
Zr]Zr
IV
) or Iodine-124 ([
124
I]I), was best suited to label chDAB4 for post-chemotherapy PET imaging of tumor-bearing mice and to determine which of two different bifunctional chelators provided optimal tumor imaging by PET using [
89
Zr]Zr
IV
-labeled chDAB4.
Methods
C57BL/6 J mice bearing subcutaneous syngeneic tumors of EL4 lymphoma were either untreated or given chemotherapy, then administered radiolabeled chDAB4 after 24 h with its biodistribution examined using PET and organ assay. We compared chDAB4 radiolabeled with [
89
Zr] Zr
IV
or [
124
I] I, or [
89
Zr]Zr-chDAB4 using either DFO-NCS or DFOSq as a chelator.
Results
After chemotherapy, [
89
Zr]Zr-chDAB4 showed higher and prolonged mean (± SD) tumor uptake of 29.5 ± 5.9 compared to 7.8 ± 1.2 for [
124
I] I -chDAB4. In contrast, antibody uptake in healthy tissues was not affected. Compared to DFO-NCS, DFOSq did not result in significant differences in tumor uptake of [
89
Zr]Zr-chDAB4 but did alter the tumor:liver ratio in treated mice 3 days after injection in favour of DFOSq (8.0 ± 1.1) compared to DFO-NCS (4.2 ± 0.7).
Conclusion
ImmunoPET using chDAB4 radiolabeled with residualizing [
89
Zr] Zr
IV
rather than [
124
I] I optimized post-chemotherapy tumor uptake. Further, PET imaging characteristics were improved by DFOSq rather than DFO-NCS. Therefore, the radionuclide/chelator combination of [
89
Zr] Zr
IV
and DFOSq is preferred for the imminent clinical evaluation of chDAB4 as a selective tumor cell death radioligand.