In Vivo Imaging of Acute Cardiac Rejection in Human Patients Using 99mTechnetium Labeled Annexin V

Kown, Murray H.; Strausś, H. William; Blankenberg, Francis G.; Berry, Gerald J.; Stafford-Cecil, Sandy; Tait, Jonathan F.; Goris, Michael L.; Robbins, Robert C.

doi:10.1034/j.1600-6143.2001.001003270.x

Cited by 53 publications

(22 citation statements)

References 35 publications

(38 reference statements)

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“…The feasibility of using labeled annexin V as an in vivo probe is well supported by previous research. In humans, Tc-labeled annexin V has been used to detect apoptosis in the hearts of patients with acute myocardial infarction (34) as well as during acute cardiac rejection (56) and in an intracardiac tumor (57). More recently, 99m Tc-labeled annexin V was used in a quantitative tumor apoptosis imaging study using singlephoton emission computed tomography in patients with head and neck carcinoma (35,36).…”

Section: Discussionmentioning

confidence: 99%

Imaging β-Cell Death With a Near-Infrared Probe

et al. 2005

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Evidence exists for an essential role of ␤-cell apoptosis in the pathology of type 1 and type 2 diabetes. Current methods for diabetes-associated apoptosis detection, however, suffer the drawbacks of relying on in situbased strategies. In this study, we attempted to measure, both in vitro and ex vivo, levels of ␤-cell apoptosis in diabetic mice using Cy5.5-labeled annexin V. We used streptozotocin-treated BALB/c mice and NOD mice of different ages as models of type 1 diabetes and db/db mice as a model of type 2 diabetes. With annexin V Cy5.5, we established differences in levels of apoptosis between diabetic and control animals. Intravenously administered annexin V Cy5.5 accumulated in pancreata of diabetic mice but not in nondiabetic controls. Furthermore, its localization was specific to apoptotic events within diabetic islets; its selectivity was supported by transferase-mediated dUTP nick-end labeling staining. Because annexin V defines an early marker of apoptosis and the developed probe is suitable for in vivo administration, it may provide a promising tool for real-time identification in intact animals of the earliest stages of diabetes-associated ␤-cell death and for tracing the events that characterize the pathology of the disease. Diabetes 54:1780 -1788, 2005

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Section: Discussionmentioning

confidence: 99%

Imaging β-Cell Death With a Near-Infrared Probe

et al. 2005

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“…As this quality is hardly affected by labeling with optical or nuclear probes, in vivo molecular imaging of cell death using Annexin A5 (Fig. 1) has been applied successfully in a variety of (patho)physiologic conditions, including cardiovascular and oncologic medicine (11,(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

Section: Annexin A5: Detection Of the Cell Death Signaturementioning

confidence: 99%

Counting Heads in the War against Cancer: Defining the Role of Annexin A5 Imaging in Cancer Treatment and Surveillance

Corsten

Hofstra²,

Narula

et al. 2006

Cancer Research

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“…Annexin V is a typical member of this protein family, which is becoming important as a means to measure cell death in vivo in cancer chemotherapy, organ transplant rejection, and myocardial infarction (5)(6)(7)(8)(9)(10), creating a need to better understand structural and functional properties relevant to its clinical use. Novel engineered forms of annexin V are being developed to improve its utility for imaging (11,12), and there has been a recent report of a single-domain version of annexin V that may be useful for imaging cell death in vivo (13).…”

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confidence: 99%

Essential Role of B-helix Calcium Binding Sites in Annexin V-Membrane Binding

Jin¹,

Smith²,

Hsieh³

et al. 2004

Journal of Biological Chemistry

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Crystal structures of annexin V have shown up to 10 bound calcium ions in three different types of binding sites, but previous work concluded that only one of these sites accounted for nearly all of the membrane binding affinity of the molecule. In this study we mutated residues contributing to potential calcium binding sites in the AB and B helices in each of the four domains (eight sites in total) and in DE helices in the first, second, and third domains (three sites in total). We measured the affinity of each protein for phospholipid vesicles and cell membranes by quantitative calcium titration under low occupancy conditions (<1% saturation of available membrane binding sites). Affinity was calculated from the midpoint and slope of the calcium titration curve and the concentration of membrane binding sites. The results showed that all four AB sites were essential for high affinity binding, as were three of the four B sites (in domains 1, 2, and 3); the DE site in the first domain made a slight contribution to affinity. Multisite mutants showed that each domain contributed additively and independently to binding affinity; in contrast, AB and B sites within the same domain were interdependent. The number of functionally important sites identified was consistent with the Hill coefficient observed in calcium titrations. This study shows an essential and previously unappreciated role for B-helix calcium binding sites in the membrane binding of annexins and indicates that all four domains of the molecule are required for maximum membrane binding affinity.The annexins are a family of calcium-dependent membranebinding proteins with diverse functions (1-4). Annexin V is a typical member of this protein family, which is becoming important as a means to measure cell death in vivo in cancer chemotherapy, organ transplant rejection, and myocardial infarction (5-10), creating a need to better understand structural and functional properties relevant to its clinical use. Novel engineered forms of annexin V are being developed to improve its utility for imaging (11,12), and there has been a recent report of a single-domain version of annexin V that may be useful for imaging cell death in vivo (13).Calcium binding sites in annexins are of three structural types: AB (or Type II), DE (or Type III), and B or ABЈ (14). In these binding sites, calcium ligands consist of one to three carbonyl oxygens from the protein backbone, and one carboxyl group from an Asp or Glu residue; sites are often named based on the domain (1 through 4) and ␣-helices (A through E), which contribute the backbone carbonyl ligands. However, the number of calcium ions observed in different structures varies widely; for example, anywhere from 2 or 3 (15, 16) to 10 (17) calcium ions have been observed in different crystal forms of annexin V. Thus, it has been difficult to determine which calcium binding sites are functionally important based on structural data alone. Previous work with annexin V mutants indicated that the AB site in domain 1 was the most impor...

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In Vivo Imaging of Acute Cardiac Rejection in Human Patients Using 99mTechnetium Labeled Annexin V

Abstract: Tc-annexin V appears to be well tolerated and may identify patients with acute cardiac rejection.

Cited by 53 publications

References 35 publications

Imaging β-Cell Death With a Near-Infrared Probe

Imaging β-Cell Death With a Near-Infrared Probe

Counting Heads in the War against Cancer: Defining the Role of Annexin A5 Imaging in Cancer Treatment and Surveillance

Essential Role of B-helix Calcium Binding Sites in Annexin V-Membrane Binding

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