PT  - JOURNAL ARTICLE
AU  - Rousseau, Jacques A.
AU  - Maier, Marcel
AU  - Ait-Mohand, Samia
AU  - Dumulon-Perreault, Véronique
AU  - Sarrhini, Otman
AU  - Tremblay, Sébastien
AU  - Rousseau, Etienne
AU  - Salzmann, Michael
AU  - Guérin, Brigitte
TI  - Antibody-Based PET Imaging of Misfolded Superoxide Dismutase 1 in an Amyotrophic Lateral Sclerosis Mouse Model
AID  - 10.2967/jnumed.124.268343
DP  - 2025 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 130--135
VI  - 66
IP  - 1
4099  - http://jnm.snmjournals.org/content/66/1/130.short
4100  - http://jnm.snmjournals.org/content/66/1/130.full
SO  - J Nucl Med2025 Jan 01; 66
AB  - Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease characterized by motor neuron loss in the motor cortex, brain stem, and spinal cord. Mutations in the superoxide dismutase 1 (SOD1) gene, resulting in misfolding of its protein product, are a common cause of ALS. Currently, there is no approved ALS diagnostic tool. Here, we present the development of a PET radiotracer, [89Zr]Zr-desferoxamine (DFO)-α-miSOD1, targeting selectively misfolded SOD1 (misSOD1). Methods: DFO-α-miSOD1 was prepared by conjugating α-miSOD1 antibody with DFO and labeled with 89Zr. A longitudinal imaging study was performed to identify the optimal mouse age and time after administration of [89Zr]Zr-DFO-α-miSOD1 for the detection of misSOD1 aggregation in transgenic mice overexpressing misSOD1 and in wild-type mice. Subsets of mice were either coinjected with an excess of α-miSOD1 or imaged with deglycosylated [89Zr]Zr-DFO-α-miSOD1 to assess target specificity. The internal radiation dose for [89Zr]Zr-DFO-α-miSOD1 was estimated by extrapolating data from mouse biodistribution experiments. Results: Imaging with [89Zr]Zr-DFO-α-miSOD1 was optimal in 136-d-old transgenic mice on day 10 after administration. Significant accumulation of [89Zr]Zr-DFO-α-miSOD1 was detected in the spinal cord and cartilage of ALS transgenic mice compared with the wild-type mice (P = 0.01). The radiotracer accumulation is selective and blockable with an excess of α-miSOD1. Deglycosylated [89Zr]Zr-DFO-α-miSOD1 results in high-contrast detection of misSOD1 but is prone to aggregation. The dosimetry for [89Zr]Zr-DFO-α-miSOD1 is comparable to that for other 89Zr-based tracers currently used in humans. Conclusion: This work thus establishes that [89Zr]Zr-DFO-α-miSOD1 PET can detect misSOD1 in transgenic mice, paving the way for application in early diagnosis of ALS and therapeutic monitoring.