[11C]PiB binding after treatment with an amyloid-beta antibody

• In several studies of anti-Aβ antibodies, the successful elimination of amyloid-beta (Aβ) plaques after treatment was indicated by substantially decreased amyloid levels in positron emission tomography (PET) imaging in Alzheimer's disease (AD) patients. However, this decrease in brain amyloid, as measured by PET, has not been matched by a similar substantial effect on cognitive function. Thus, we used one of the amyloid PET ligands, [11C]PiB, to evaluate if the decrease of the PET signal is due to the removal of amyloid pathology or if repeated antibody administration instead blocks [11C]PiB binding sites on the Aβ deposits in brain tissue.First, the ability of mAb158 (the murine version of anti-Aβ antibody lecanemab) to block thioflavin-S (ThS, structure similar to PiB) binding to Aβ deposits was investigated in mouse brain sections from 19-21 months old transgenic mice with Aβ pathology (tg-ArcSwe). Next, tg-ArcSwe mice received weekly treatment with 50 mg/kg of mAb158 or PBS for 3 weeks before i.v. administration of [11C]PiB. At 40 min post-injection, brain sections were prepared from the mice, and ex vivo autoradiography was carried out. Concentrations of total Aβ1-40 and Aβ1-42 in the brain were further measured by enzyme-linked immunosorbent assay (ELISA) and staining.Group comparison showed that the integrated density of in vitro ThS staining was similar in brain sections pre-incubated with PBS and mAb158. Ex vivo autoradiography after mAb158 treatment and [11C]PiB injection indicated that [11C]PiB binding in general was similar in mAb158- and PBS-treated animals but a small tendency of reduced signals existed in the mAb158-treated animals. The brain Aβ1-40 and Aβ1-42 concentrations measured by ELISA were similar in both treatment groups.The study suggested that [11C]PiB binding to Aβ deposits reflected brain Aβ load and that plaque decoration by administering therapeutic antibodies only had a limited blocking effect on amyloid radioligand binding.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Nyckelord

Amyloid PET

[11C]PiB

AD

antibody treatment

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vet (ämneskategori)

ovr (ämneskategori)