Noninvasive visualization of tumoral fibrin deposition using a peptidic fibrin-binding single photon emission computed tomography tracer.
Fibrin deposition plays an important role in the formation of mature tumor stroma and provides a facilitating scaffold for tumor angiogenesis. This study investigates the potential of the (111)In-labeled fibrin-binding peptide EPep for SPECT imaging of intratumoral fibrin deposition. (111)In-EPep and negative control (111)In-NCEPep were synthesized and characterized in vitro. In vivo SPECT images and ex vivo biodistribution profiles and autoradiographs were obtained in a fibrin-rich BT-20 breast cancer mouse model. Furthermore, biodistribution profiles were obtained in the fibrin-poor MDA-MD-231 model. In vitro, (111)In-EPep displayed significantly more binding than (111)In-NCEPep toward human and mouse derived fibrin. SPECT/CT images displayed a marked SPECT signal in the tumor area for BT-20 tumor bearing mice injected with EPep but not for mice injected with NCEPep. Biodistribution profiles of BT-20 tumor bearing mice 3 h post-tracer injection showed significantly higher tumor uptake for EPep with respect to NCEPep (0.39 ± 0.14 and 0.11 ± 0.03% ID g(-1), respectively), whereas uptake in other organs was similar for EPep and NCEPep. Autoradiography of BT-20 tumor sections displayed a high signal for EPep which colocalized with intratumoral fibrin deposits. Histological evaluation of MDA-MB-231 tumor sections displayed no significant tumor stroma and only minute fibrin deposits. Biodistribution profiles in MDA-MB-231 tumor bearing mice 3 h post-injection showed EPep tumor uptake (0.14 ± 0.04% ID g(-1)) which was significantly lower with respect to EPep BT-20 tumor uptake, indicating fibrin-specificity of EPep tumoral uptake. In conclusion, this work demonstrates the potential of EPep SPECT imaging for visualization of tumoral fibrin deposition.
†Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.
Lucas W E
LW
Starmans
†Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.
Tiemen
T
van Mourik
‡Oncology Solutions, Philips Research, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.
Raffaella
R
Rossin
‡Oncology Solutions, Philips Research, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.
Iris
I
Verel
†Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.
Klaas
K
Nicolay
†Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.|‡Oncology Solutions, Philips Research, High Tech Campus 11, 5656 AE, Eindhoven, The Netherlands.
Holger
H
Grüll
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging; D010455:Peptides / Q000378:metabolism*; D011859:Radiography; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D010455:Peptides; D005337:Fibrin
cancer; fibrin; fibrin-binding peptide; single photon emission computed tomography (SPECT); tumor stroma