Monoclonal Antibodies: What the Diagnostic Neuroradiologist Needs to Know

Abstract

Monoclonal antibodies have become increasingly popular as novel therapeutics against a variety of diseases due to their specificity, affinity, and serum stability. Due to the nearly infinite repertoire of monoclonal antibodies, their therapeutic use is rapidly expanding, revolutionizing disease course and management, and what is now considered experimental therapy may soon become approved practice. Therefore, it is important for radiologists, neuroradiologists, and neurologists to be aware of these drugs and their possible different imaging-related manifestations, including expected and adverse effects of these novel drugs. Herein, we review the most commonly used monoclonal antibody-targeted therapeutic agents, their mechanism of action, clinical applications, and major adverse events with a focus on neurologic and neurographic effects and discuss differential considerations, to assist in the diagnosis of these conditions.

FIG 1.

Hypophysitis induced by anti-CTLA-4 mAbs. This 61-year-old woman with metastatic melanoma underwent adjuvant treatment with ipilimumab. A, Sagittal T1 fast-spoiled gradient recalled image cut through the midline, postgadolinium, at initiation of treatment in the patient with a normal-for-age pituitary gland. MR imaging 6 months later (B–D) demonstrates a markedly thickened, densely enhancing pituitary gland in keeping with ipilimumab-induced hypophysitis.

FIG 2.

NTZ-induced PML. PML in a 52-year-old male patient with Crohn disease treated with NTZ. FLAIR (A and F), enhanced T1 (B and G), SWI (C and H), DWI (D and I), and ADC maps (E and J) at ganglionic (A–E) and supraganglionic (F–J) levels demonstrate the typical imaging features of PML with subcortical U-fiber involvement, lack of enhancement, and asymmetric involvement of the white matter.

FIG 3.

PML-IRIS after cessation of NTZ treatment. PML-IRIS in the same patient as depicted in Fig 2 following cessation of NTZ. The condition of the patient deteriorated clinically, prompting additional imaging that now demonstrates a “leading edge” of demyelination toward the white matter, mild enhancement, and DWI hypersignal, in keeping with cellular infiltration.

FIG 4.

ARIA-E on follow-up. T2-weighted FLAIR scans at baseline (A and D), after 7 months of aducanumab treatment (B and E), and on follow-up 2 months later (C and F) demonstrate, in this 81-year-old patient who remained clinically stable, new development of edematous changes in the left occipital and parietal cortical and subcortical regions (arrows), which spontaneously resolved, in keeping with ARIA-E.

FIG 5.

ARIA-H. In this 80-year old woman treated for amnestic mild cognitive impairment with aducanumab, serial imaging demonstrates, in the asymptomatic patient, new foci of blooming artifacts within the left frontal sulcus compared with the baseline scan (A and B; FLAIR and T2 gradient echo sequences). On follow-up 3 months later (C and D), note T2-weighted FLAIR hypersignal surrounding the left superior frontal sulcus (arrow in C), where mild pial siderosis is seen (arrow in D), in keeping with ARIA-H.

FIG 6.

Demyelinating lesions after anti-TNF-α AE. This 36-year-old female patient with ankylosing spondylitis was treated with adalimumab and had cognitive decline. MR imaging (A–D: T2 weighted FLAIR, E: DWI, F: Contrast enhanced T1) demonstrates multiple demyelinating plaques with very subtle contrast enhancement (arrow, F).