Imaging VEGF Receptors and αvβ3 Integrins in a Mouse Hindlimb Ischemia Model of Peripheral Arterial Disease

Abstract

In a mouse hindlimb ischemia model of peripheral artery disease, [Tc]scV SPECT tracer-targeting VEGF receptors showed a more robust signal than [Tc]RGD tracer-targeting αβ. Immunofluorescent analysis suggests that uptake of [Tc]scV and [Tc]RGD in damaged tissue is due to non-overlapping cell populations and reflects different dynamic processes and that enhanced uptake of [Tc]scV may be due to the presence of VEGF receptors on additional cell types.

VEGF receptor targeted imaging of angiogenic response to limb ischemia in diabetic vs. non-diabetic Yucatan minipigs

“…The radiotracer we used to image angiogenesis, [ 99m Tc]DOTA-PEG-scVEGF, is based on an engineered single-chain (sc) recombinant version of VEGF121, site-specifically derivatized with PEGylated chelator DOTA for radiolabeling with 99m Tc (14,15). scV/Tc and its receptor-selective versions show nanomolar affinity to VEGFR-1 and VEGFR-2 is readily internalized upon binding to the VEGF receptors, and it reliably detects VEGF receptor expression in murine models of atherosclerosis and angiogenesis [16,27]. This is the first study to show feasibility of molecularly targeting angiogenesis in response to vascular occlusion in a diabetic large animal model.…”

“…On day 7 after vascular occlusion, pigs were sedated, intubated, and anesthetized as described above. 99m Tclabeled scV was prepared as previously described [16]. A dose of 296.37 ± 82.88 MBq (8.01 ± 2.24 mCi) of scV/Tc was injected through the ear vein catheter.…”

“…The radiotracer targeting VEGF receptors showed a more robust signal than the RGD tracer targeting α v β 3 . Immunofluorescense analysis indicated that differences in overall uptake of these two radiotracers in ischemic tissue can be explained by differences in affinity for the two probes to nonoverlapping cell populations with uptake of scV/Tc seen on additional cell types [16]. The hindlimb vascular and muscle anatomy in a pig is closer to humans than in a mouse.…”

“…An alternative target for molecular imaging is receptors for VEGF released locally in response to vascular occlusion [14,15]. We previously compared [ 99m Tc]DOTA-PEG-scVEGF (scV/Tc) tracer targeting VEGF receptors 1 and 2 vs. 99m Tc-labeled RGD-based tracer, targeting α v β 3 integrins in a mouse hindlimb ischemia model [16]. The radiotracer targeting VEGF receptors showed a more robust signal than the RGD tracer targeting α v β 3 .…”

Multi-modality imaging for assessment of the microcirculation in peripheral artery disease: Bench to clinical practice

“…Using SPECT imaging of [ 99m Tc]DOTA-PEG-scVEGF that targets the VEGF receptor, Tekabe et al found a stronger signal for evaluating angiogenesis compared to another [ 99m Tc] radiotracer targeting the α V β 3 integrin . in a mice model of limb ischemia using femoral artery ligation [ 140 ]. Interestingly, immunofluorescent analysis revealed the uptake of these radiotracers is non-overlapping, and could potentially be used to assess different cell types and processes [ 140 ].…”