Multimodal Molecular Imaging Reveals High Target Uptake and Specificity of ¹¹¹In- and ⁶⁸Ga-Labeled Fibrin-Binding Probes for Thrombus Detection in Rats

Representative PET and SPECT images (crush model, 30–90 min after injection) showing persistent thrombus signal (arrow) after injection of ⁶⁸Ga-FBP14 (n = 5) and ¹¹¹In-FBP15 (n = 4) but not for ^99mTc-FP16 (n = 3). PET and SPECT quantification revealed high target radioactivity for ⁶⁸Ga-FBP14 and ¹¹¹In-FBP15 compared with background tissues, resulting in high thrombus-to-background radioactivity ratios. ***P < 0.001. ns = not significant.

(A) Biodistribution at 120 min (crush model; ⁶⁸Ga-FBP14, n = 5; ¹¹¹In-FBP15, n = 8; ^99mTc-FBP16, n = 6). (B) Representative autoradiographs of excised injured and contralateral carotid arteries after injection of ¹¹¹In-FBP15 and ipsilateral-to-contralateral ratios for each probe (n = 5–6/probe). (C) Pharmacokinetic data from ex vivo blood analyses (⁶⁸Ga-FBP14, n = 5; ¹¹¹In-FBP15, n = 8; ^99mTc-FBP16, n = 4). ○ = total radioactivity in plasma; ● = functional probe. *P < 0.05. ***P < 0.001. ns = not significant.

(A) CT, PET, and fused images from animal injected with ⁶⁴Cu-d-Cys-FBP8 after carotid crush injury (n = 2). Contrast-enhanced CT angiography was used to detect common carotid artery (thin arrow). Thrombus location could not be detected by PET. (B) Time–radioactivity curves obtained from PET imaging, mean radioactivity values (30–90 min after injection), and representative photograph and autoradiograph of ipsilateral (ipsi) and contralateral (contra) carotid arteries showing comparable radioactivity levels between thrombus and background. (C) PET/CT imaging (n = 3) after sequential injection of ⁶⁴Cu-d-Cys-FBP8, followed by injection of its active analog ⁶⁴Cu-FBP8. Thrombus uptake was detected only after injection of ⁶⁴Cu-FBP8 (blue arrow). (D) Statistically significant difference in thrombus versus contralateral artery uptake for ⁶⁴Cu-FBP8 but not ⁶⁴Cu-d-Cys-FBP8. In vitro binding studies of blood plasma incubated with immobilized fibrin showed significantly lower binding for ⁶⁴Cu-d-Cys-FBP8 than ⁶⁴Cu-FBP8 (n = 2). **P < 0.01. ***P < 0.001.