Prospective of 68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation

Abstract

During the last decade, the utilization of ⁶⁸Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of ⁶⁸Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management.

Figure 1

PET images of the distribution of [⁶⁸Ga]Ga-DOTAVAP-P1, [⁶⁸Ga]Ga-DOTAVAP-PEG-P1, and [⁶⁸Ga]Ga-DOTA-Siglec-9 in turpentine-induced rat model of sterile inflammation. All three peptide analogues showed target-to-nontarget ratio above 6 with rapid accumulation in the inflammation site and renal clearance. Adapted from [57].

Figure 2

Accumulation of [⁶⁸Ga]Ga-DOTA-folate (a) in the site of inflammation of rat inflammatory paw model induced by subcutaneously injected Complete Freund's Adjuvant (b). Adapted from [61].

Figure 3

Intense atherosclerotic inflammation (white arrows) was detected by [⁶⁸Ga]Ga-DOTA-TATE in a patient with acute coronary syndrome. Adapted from [65].

Figure 4

Left panel presents maximum intensity projection images of [⁶⁸Ga]Ga-DOTA-TBIA101 distribution in a healthy mouse (a) and a mouse with muscular infection site (MIS) in the right hind muscle tissue (white arrows). Right panel presents coronal (c), sagittal (d), and axial (e) images with uptake in the MIS (white arrow) and absence of the uptake in the contralateral muscle tissue. Ki and Bl stand, respectively, for kidney and bladder. Reproduced from [73].

Figure 5

Molecular structure of [⁶⁸Ga]Ga-triacetylfusarinine C (a) used for the in vivo imaging of a rat with Aspergillus fumigatus infection (b) and negative control of noninfected rat (c). White arrows point at the infected (b) and normal (c) lungs. Adapted from [76].

Figure 6

[⁶⁸Ga]Ga-citrate PET/CT examination of a patient affected by acute osteomyelitis before (left panel) and after (right panel) surgical curettage showing uptake in the transaxial (a, c) and 3D reconstruction images (b, d; red area). Absence of the uptake after the therapy confirms complete response to the treatment. Adapted from [19].

Figure 7

Vertebral osteomyelitis (spondylodiscitis; red arrowheads) and abscesses in the iliopsoas and paravertebral area (red arrows) were detected by [⁶⁸Ga]Ga-citrate in a patient admitted to the hospital with back pain and general symptoms. The PET acquisition was performed 88 min after administration of 245 MBq of [⁶⁸Ga]Ga-citrate. Adapted from [80].

Figure 8

Schematic presentation of pretargeting techniques: (a) bispecific antibodies engineered to specifically bind with radiolabelled hapten molecules; (b) bioorthogonal click chemistry for fast and specific covalent binding between, for example, a trans-cyclooctene functionalized antibody and a radiolabelled tetrazine; (c) interaction between antibody-(strept)avidin conjugate and radiolabelled biotin utilizing extremely high affinity of (strept)avidin and biotin.