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Targeted molecular imaging of angiogenesis in PET and SPECT: a review.

Stacy MR, Maxfield MW, Sinusas AJ - Yale J Biol Med (2012)

Bottom Line: Over the past few decades, there have been significant advancements in the imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPECT).Though the aforementioned techniques have benefits and consequences, they enable scientists and clinicians to identify regions that are vulnerable to or have been exposed to ischemic injury via non-invasive means.This literature review highlights the advancements in molecular imaging techniques and specific probes as they pertain to the process of angiogenesis in cardiovascular disease.

View Article: PubMed Central - PubMed

Affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. mitchel.stacy@yale.edu

ABSTRACT
Over the past few decades, there have been significant advancements in the imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPECT). These changes have allowed for the targeted imaging of cellular processes and the development of hybrid imaging systems (e.g., SPECT/CT and PET/CT), which provide both functional and structural images of biological systems. One area that has garnered particular attention is angiogenesis as it relates to ischemic heart disease and limb ischemia. Though the aforementioned techniques have benefits and consequences, they enable scientists and clinicians to identify regions that are vulnerable to or have been exposed to ischemic injury via non-invasive means. This literature review highlights the advancements in molecular imaging techniques and specific probes as they pertain to the process of angiogenesis in cardiovascular disease.

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In vivo microSPECT-CT imaging and radiotracerquantification post-myocardial infarction. a) Thallium-201 perfusion(top row, green) and αvβ3 integrin targeted imaging (middle row, red) withSPECT-CT in an IGF-1 treated rat at 4 weeks post-MI. Bottom row represents fusedimage with reference contrast CT image (grayscale). b) Gamma countprofiles of thallium-201 (open circles) and 99mTc-NC100692 (solidcircles) from middle myocardial sections. (reprinted with permission of[29])
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Figure 3: In vivo microSPECT-CT imaging and radiotracerquantification post-myocardial infarction. a) Thallium-201 perfusion(top row, green) and αvβ3 integrin targeted imaging (middle row, red) withSPECT-CT in an IGF-1 treated rat at 4 weeks post-MI. Bottom row represents fusedimage with reference contrast CT image (grayscale). b) Gamma countprofiles of thallium-201 (open circles) and 99mTc-NC100692 (solidcircles) from middle myocardial sections. (reprinted with permission of[29])

Mentions: 99mTc-NC100692 (maraciclatide®) is a technetium-labeled cyclic RGD peptidethat has been used in a variety of SPECT studies to noninvasively assessangiogenesis [2]. The NC100692compound has a high affinity for the αvβ3 integrin, is metabolically stable, and hasa biodistribution and kinetics that are favorable for SPECT imaging. Increased focalactivity of 99mTc-NC100692 has been demonstrated with SPECT at 3 and 7days post-femoral artery ligation in a murine model of hind limb ischemia[24]. These results werefurther confirmed by the close correlation of ex vivo tissueanalysis (gamma counting) and immunofluorescence staining. A similar study using amurine model of hind limb ischemia examined peripheral angiogenesis in wild-type andendothelial nitric oxide synthase (eNOS) deficient animals with microSPECT-CT (Figure 2) [9]. This study, directed at serial quantitative evaluation ofangiogenesis, revealed decreased uptake of the compound within ischemic regions ofthe eNOS deficient mice when compared to wild-type. Both groups, however, exhibitedthe largest retention of 99mTc-NC100692 at 7 days post-femoral arteryocclusion, as indicated by ex vivo gamma counting of ischemictissue. Other studies using microSPECT-CT have confirmed the uptake of99mTc-NC100692 within mice [12] and rats [29,52] followingsurgically induced myocardial infarction. Dobrucki et al. used99mTc-NC100692 microSPECT imaging to evaluate the effects of gene therapydirected at stimulating angiogenesis. In this study, focal uptake of99mTc-NC100692 was seen in the peri-infarct region in association withaccelerated angiogenesis induced by intramyocardial injection of a viral vector toupregulate expression of insulin-like growth factor (IGF-1) in rats, with furthervalidation provided via gamma counting of heart tissue (Figure 3) [29]. The clinical translation of cardiovascular SPECT imaging with99mTc-NC100692 was recently shown (Figure 4) and demonstrated the feasibility and applicability of thistargeted imaging approach for broad scale clinical application in ischemic heartdisease [66].


Targeted molecular imaging of angiogenesis in PET and SPECT: a review.

Stacy MR, Maxfield MW, Sinusas AJ - Yale J Biol Med (2012)

In vivo microSPECT-CT imaging and radiotracerquantification post-myocardial infarction. a) Thallium-201 perfusion(top row, green) and αvβ3 integrin targeted imaging (middle row, red) withSPECT-CT in an IGF-1 treated rat at 4 weeks post-MI. Bottom row represents fusedimage with reference contrast CT image (grayscale). b) Gamma countprofiles of thallium-201 (open circles) and 99mTc-NC100692 (solidcircles) from middle myocardial sections. (reprinted with permission of[29])
© Copyright Policy - open access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3313541&req=5

Figure 3: In vivo microSPECT-CT imaging and radiotracerquantification post-myocardial infarction. a) Thallium-201 perfusion(top row, green) and αvβ3 integrin targeted imaging (middle row, red) withSPECT-CT in an IGF-1 treated rat at 4 weeks post-MI. Bottom row represents fusedimage with reference contrast CT image (grayscale). b) Gamma countprofiles of thallium-201 (open circles) and 99mTc-NC100692 (solidcircles) from middle myocardial sections. (reprinted with permission of[29])
Mentions: 99mTc-NC100692 (maraciclatide®) is a technetium-labeled cyclic RGD peptidethat has been used in a variety of SPECT studies to noninvasively assessangiogenesis [2]. The NC100692compound has a high affinity for the αvβ3 integrin, is metabolically stable, and hasa biodistribution and kinetics that are favorable for SPECT imaging. Increased focalactivity of 99mTc-NC100692 has been demonstrated with SPECT at 3 and 7days post-femoral artery ligation in a murine model of hind limb ischemia[24]. These results werefurther confirmed by the close correlation of ex vivo tissueanalysis (gamma counting) and immunofluorescence staining. A similar study using amurine model of hind limb ischemia examined peripheral angiogenesis in wild-type andendothelial nitric oxide synthase (eNOS) deficient animals with microSPECT-CT (Figure 2) [9]. This study, directed at serial quantitative evaluation ofangiogenesis, revealed decreased uptake of the compound within ischemic regions ofthe eNOS deficient mice when compared to wild-type. Both groups, however, exhibitedthe largest retention of 99mTc-NC100692 at 7 days post-femoral arteryocclusion, as indicated by ex vivo gamma counting of ischemictissue. Other studies using microSPECT-CT have confirmed the uptake of99mTc-NC100692 within mice [12] and rats [29,52] followingsurgically induced myocardial infarction. Dobrucki et al. used99mTc-NC100692 microSPECT imaging to evaluate the effects of gene therapydirected at stimulating angiogenesis. In this study, focal uptake of99mTc-NC100692 was seen in the peri-infarct region in association withaccelerated angiogenesis induced by intramyocardial injection of a viral vector toupregulate expression of insulin-like growth factor (IGF-1) in rats, with furthervalidation provided via gamma counting of heart tissue (Figure 3) [29]. The clinical translation of cardiovascular SPECT imaging with99mTc-NC100692 was recently shown (Figure 4) and demonstrated the feasibility and applicability of thistargeted imaging approach for broad scale clinical application in ischemic heartdisease [66].

Bottom Line: Over the past few decades, there have been significant advancements in the imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPECT).Though the aforementioned techniques have benefits and consequences, they enable scientists and clinicians to identify regions that are vulnerable to or have been exposed to ischemic injury via non-invasive means.This literature review highlights the advancements in molecular imaging techniques and specific probes as they pertain to the process of angiogenesis in cardiovascular disease.

View Article: PubMed Central - PubMed

Affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA. mitchel.stacy@yale.edu

ABSTRACT
Over the past few decades, there have been significant advancements in the imaging techniques of positron emission tomography (PET) and single photon emission tomography (SPECT). These changes have allowed for the targeted imaging of cellular processes and the development of hybrid imaging systems (e.g., SPECT/CT and PET/CT), which provide both functional and structural images of biological systems. One area that has garnered particular attention is angiogenesis as it relates to ischemic heart disease and limb ischemia. Though the aforementioned techniques have benefits and consequences, they enable scientists and clinicians to identify regions that are vulnerable to or have been exposed to ischemic injury via non-invasive means. This literature review highlights the advancements in molecular imaging techniques and specific probes as they pertain to the process of angiogenesis in cardiovascular disease.

Show MeSH
Related in: MedlinePlus