Molecular Imaging of Inflammation: Current Status

Abstract

The ability to image inflammation in vivo can improve our understanding of the pathophysiology underlying various disease etiologies, including cancer, atherosclerosis, and neurodegeneration. A great wealth of preclinical and translational research has been and is currently being developed to decipher the involvement of the immune system in disease pathophysiology, quantify the course of a disease, and visualize the potential detrimental effects of excessive inflammation. Down the road, the ultimate goal is to have clinical noninvasive in vivo imaging biomarkers of inflammation that will help diagnose disease, establish prognosis, and gauge response to preventative and therapeutic strategies.

Keywords: MRI; PET; inflammation; iron oxide nanoparticles; molecular imaging.

Figure 1

Anti-CD4 small-animal PET imaging (using ⁸⁹Zr-malDFO-GK1.5 cys-diabodies, where malDFO is N-(3,11,14,22,25,33-hexaoxo-4,10,15,21,26, 32-hexaaaza-10,21,32-trihydroxytetratriacontane) maleimide) of T-lymphocytes in C57BL/6 wild-type, CD4-blocked, and CD4-depleted mice at 4, 8, and 22 h after injection. Images are 25-mm maximum-intensity projections. Compared with wild-type mice, both CD4-blocked and CD4-depleted animals lack uptake in axillary lymph nodes (ALN), cervical lymph nodes (CLN), inguinal lymph nodes (ILN), popliteal lymph nodes (PLN), and spleen (Sp). B 5 bone; ID 5 injected dose; K 5 kidney; Li 5 liver. (Adapted from (11).)

Figure 2

Axial MR images of inflammation in brain of young woman with multiple sclerosis. (A) Unenhanced T2-weighted image shows multiple hyperintense lesions. (B) Gadolinium-enhanced T1-weighted image before injection of USPIO shows 3 enhancing lesions (arrows). (C) At 24–48 h after injection, the original 3 lesions are seen along with 3 additional lesions (arrows). (Adapted with permission of (20).)

Figure 3

⁶⁴Cu-DOTATATE PET images of patient with Framingham risk score of 30 (A) and patient with Framingham risk score of 2 (B). High focal uptake is seen in thoracic aorta of first patient, compared with lower and more diffuse uptake in second patient. (Adapted from (26).)

Figure 4

PET/CT imaging of lung inflammation. ⁶⁸Ga-BMV101 PET/CT probe (targeting cysteine cathepsins, which are highly expressed in activated macrophages) was injected intravenously, and images were collected 2.5 h later. Patient with idiopathic pulmonary fibrosis (IPF) shows increased accumulation in fibrotic regions, but patient with unclassified fibrosis shows no significant increase compared with normal-lung control. (Adapted with permission of (35).)