Rodent biodistribution and dosimetry of the PET radioligands [18F]CHDI-385 and [18F]CHDI-386 targeting mutant huntingtin aggregates.

BACKGROUND

Huntington's disease is a neurodegenerative condition resulting from an expanded CAG repeat in the huntingtin gene that produces a mutant form of the huntingtin protein (mHTT). In this study we estimated the radiation safety of two structurally related mHTT radioligands, [18F]CHDI-385 and [18F]CHDI-386, by evaluating the in vivo and ex vivo dosimetry of both radioligands using CD-1 Swiss mice.

METHODS

We used adult male and female CD-1 Swiss mice (n = 15 per sex/radioligand) to assess in vivo positron emission tomography/computed tomography (PET/CT) imaging-based and ex vivo biodistribution-based tracer distribution of the radioligands at 30-, 60-, 120-, 240-, and 360-min post-radioligand injection. Organ activity was quantified, and the residence time was extrapolated to human phantoms. The absorbed and effective doses were estimated using OLINDA/EXM 2.2 and IDAC-Dose2.1.

RESULTS

Both radioligands, [18F]CHDI-385 and [18F]CHDI-386, showed high uptake in the gallbladder and urinary bladder, with a slow washout in most organs. The colon wall received the highest equivalent organ dose for both modalities. Ex vivo effective dose estimates were 15.4 μSv/MBq for [18F]CHDI-385 and 16.3 μSv/MBq for [18F]CHDI-386, while in vivo effective dose estimates were 18.5 μSv/MBq and 18.7 μSv/MBq, respectively.

CONCLUSION

[18F]CHDI-385 and [18F]CHDI-386 dosimetry results showed absorbed and effective doses in acceptable range and below the recommended limits. An injection of 370 MBq (10 mCi) in humans is estimated to result in highest (in vivo) effective doses of 6.85 mSv for [18F]CHDI-385 and 6.92 mSv for [18F]CHDI-386.