Noninvasive Imaging of Activated Complement in Ischemia-Reperfusion Injury Post-Cardiac Transplant

Area of Science:

• Transplantation immunology
• Medical imaging
• Complement system

Background:

• Ischemia-reperfusion injury (IRI) is a significant challenge in solid organ transplantation.
• Complement activation, particularly involving C3, plays a critical role in IRI.
• Noninvasive methods are needed to monitor complement activation and assess transplant damage.

Purpose of the Study:

• To evaluate the utility of (99m) Tc-recombinant complement receptor 2 ((99m) Tc-rCR2) for noninvasive detection of complement activation in cardiac transplantation-induced IRI.
• To compare the efficacy of (99m) Tc-rCR2 with a control in murine models.

Main Methods:

• Murine cardiac transplantation model with induced IRI.
• Noninvasive imaging using single photon emission computed tomography (SPECT) and CT with (99m) Tc-rCR2.
• Comparison groups included C3-deficient mice and mice injected with an irrelevant protein ((99m) Tc-PSMA).
• Histology and autoradiography were used for confirmation.

Main Results:

• Significant uptake of (99m) Tc-rCR2 was observed in transplanted hearts with IRI compared to control groups (C3(-/-) mice and (99m) Tc-PSMA).
• The transplanted heart to muscle uptake ratio of (99m) Tc-rCR2 was significantly higher in the IRI group.
• Histological and autoradiographic analyses confirmed the imaging findings.

Conclusions:

• (99m) Tc-rCR2 effectively detects complement activation post-IRI in cardiac transplantation.
• This imaging agent holds potential for noninvasively quantifying transplant damage severity due to complement activation.