Imaging and dosimetry of 99mTc EC annexin V: Preliminary clinical study targeting apoptosis in breast tumors

Kurihara, Hiroaki; Yang, David J.; Cristofanilli, Massimo; Erwin, William D.; Yu, Dongfang; Kohanim, Saady; Mendez, Richard; Kim, E. Edmund

doi:10.1016/j.apradiso.2008.01.012

Cited by 44 publications

(36 citation statements)

References 29 publications

(29 reference statements)

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“…Annexin-V binds phosphatidylserine with high affinity (5) and has been used widely as a preclinical tool for detecting cell death, both in vitro and in vivo. However, binding of annexin-V to tumor tissue after therapy is thought not to be entirely phosphatidylserine-specific, possibly explaining the limited success of annexin-V in the clinic, which has been hampered by high levels of nonspecific binding to viable tissues, including the liver, gut, and kidneys (29). Modifications to annexin-V have shown limited improvements in biodistribution or contrast agent performance in vivo (8).…”

Section: Discussionmentioning

confidence: 99%

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

et al. 2017

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Cell death is an important target for imaging the early response of tumors to treatment. We describe here the validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of synaptotagmin-I. Methods: The capability of nearinfrared fluorophore-labeled and 99m In-labeled derivatives of C2Am for imaging tumor cell death, using planar near-infrared fluorescence imaging and SPECT, respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft. Results: The fluorophorelabeled C2Am derivative showed predominantly renal clearance and high specificity and sensitivity for detecting low levels of tumor cell death (2%-5%). There was a significant correlation (R . 0.9, P , 0.05) between fluorescently labeled C2Am binding and histologic markers of cell death, including cleaved caspase-3, whereas there was no such correlation with a site-directed mutant of C2Am (iC2Am) that does not bind phosphatidylserine. 99m In-C2Am also showed favorable biodistribution profiles, with predominantly renal clearance and low nonspecific retention in the liver and spleen at 24 h after probe administration. 99m In-C2Am generated tumor-to-muscle ratios in drug-treated tumors of 4.3· and 2.2·, respectively, at 2 h and 7.3· and 4.1·, respectively, at 24 h after administration. Conclusion: Given the favorable biodistribution profile of 99m In-labeled C2Am, and their ability to produce rapid and cell death-specific image contrast, these agents have potential for clinical translation.

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Section: Discussionmentioning

confidence: 99%

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

et al. 2017

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“…Similar good results were achieved when patients with follicular lymphomas were treated with radiation only . Meanwhile, radiolabelled annexin A5 was used for monitoring of chemotherapy and radio-chemotherapy in several studies with different tumour types (Kartachova et al 2004;Hoebers et al 2008;Kurihara et al 2008). In addition to oncology, apoptosis imaging with technetium annexin A5 allowed vulnerable atherosclerotic plaques to be distinguished from stable plaques in carotid arteries of patients undergoing carotid endarterectomy.…”

Section: Targeted Nanosensors For Imaging Apoptosismentioning

confidence: 99%

Bioresponsive nanosensors in medical imaging

Schellenberger

2009

J. R. Soc. Interface.

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Superparamagnetic iron oxide nanoparticles have been established as sensitive probes for magnetic resonance imaging (MRI). While the majority of specific nanosensors are based on sterically stabilized iron oxide particles, the focus of this review is on the use of very small iron oxide particles (VSOPs) that are electrostatically stabilized by an anionic citrate acid shell. We used VSOPs to develop target-specific as well as protease-activatable nanosensors for molecular MRI.

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“…With these tissues used as internal controls, PET images in several subjects reveal elevated uptake of 18 F-CP-18 in both shoulder cartilage and mammary glands relative to noncaspase-expressing tissue (e.g., muscle), consistent with differences in caspase-3 expression levels observed across such tissues (31). As a second confirmation that 18 F-CP-18 is targeting tissue apoptosis, the SPECT apoptosis imaging agent 99m Tc-EC annexin V also appeared to exhibit uptake in shoulder cartilage similar to 18 F-CP18, suggesting that both tracers target an overlapping pathology (32). The biodistribution and radiation dosimetry of 18 F-CP-18 are likely compatible with its use as a PET apoptosis imaging agent.…”

Section: Discussionmentioning

confidence: 56%

Biodistribution and Radiation Dosimetry of ¹⁸F-CP-18, a Potential Apoptosis Imaging Agent, as Determined from PET/CT Scans in Healthy Volunteers

et al. 2013

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F18-fluoropropyl)-1H-1,2,3-triazol-1-yl)acetamido)methyl)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxamido)- 24-isopropyl-18-methyl-17,20,23,26, 29-pentaoxo-4,7,10,13-tetraoxa-16,19,22,25,28-pentaazadotriacontane-1,32-dioicacid, is being evaluated as a tissue apoptosis marker for PET imaging. The purpose of this study was to determine the biodistribution and estimate the normal-organ radiation-absorbed doses and effective dose from 18 F-CP-18. Methods: Successive wholebody PET/CT scans were obtained at approximately 7, 45, 90, 130, and 170 min after intravenous injection of 18 F-CP-18 in 7 healthy human volunteers. Blood samples and urine were collected between the PET/CT scans, and the biostability of 18 F-CP-18 was assessed using high-performance liquid chromatography. The PET scans were analyzed to determine the radiotracer uptake in different organs. OLINDA/EXM software was used to calculate human radiation doses based on the biodistribution of the tracer. Results: 18 F-CP-18 was 54% intact in human blood at 135 min after injection. The tracer cleared rapidly from the blood pool with a half-life of approximately 30 min. Relatively high 18 F-CP-18 uptake was observed in the kidneys and bladder, with diffuse uptake in the liver and heart. The mean standardized uptake values (SUVs) in the bladder, kidneys, heart, and liver at around 50 min after injection were approximately 65, 6, 1.5, and 1.5, respectively. The calculated effective dose was 38 6 4 mSv/MBq, with the urinary bladder wall having the highest absorbed dose at 536 6 61 mGy/MBq using a 4.8-h bladder-voiding interval for the male phantom. For a 1-h voiding interval, these doses were reduced to 15 6 2 mSv/MBq and 142 6 15 mGy/MBq, respectively. For a typical injected activity of 555 MBq, the effective dose would be 21.1 6 2.2 mSv for the 4.8-h interval, reduced to 8.3 6 1.1 mSv for the 1-h interval. Conclusion: 18 F-CP-18 cleared rapidly through the renal system. The urinary bladder wall received the highest radiation dose and was deemed the critical organ. Both the effective dose and the bladder dose can be reduced by frequent voiding. From the radiation dosimetry perspective, the apoptosis imaging agent 18 F-CP-18 is suitable for human use.

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Imaging and dosimetry of 99mTc EC annexin V: Preliminary clinical study targeting apoptosis in breast tumors

Abstract: Background-Early detection of cellular events is important to predict the outcome of the patients. This study was aimed to use 99m Tc EC-annexin V to image tumor cells undergoing apoptosis.

Cited by 44 publications

References 29 publications

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

Bioresponsive nanosensors in medical imaging

Biodistribution and Radiation Dosimetry of ¹⁸F-CP-18, a Potential Apoptosis Imaging Agent, as Determined from PET/CT Scans in Healthy Volunteers

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Imaging and dosimetry of 99mTc EC annexin V: Preliminary clinical study targeting apoptosis in breast tumors

Abstract: Background-Early detection of cellular events is important to predict the outcome of the patients. This study was aimed to use 99m Tc EC-annexin V to image tumor cells undergoing apoptosis.

Cited by 44 publications

References 29 publications

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

Rapid Imaging of Tumor Cell Death In Vivo Using the C2A Domain of Synaptotagmin-I

Bioresponsive nanosensors in medical imaging

Biodistribution and Radiation Dosimetry of 18F-CP-18, a Potential Apoptosis Imaging Agent, as Determined from PET/CT Scans in Healthy Volunteers

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Biodistribution and Radiation Dosimetry of ¹⁸F-CP-18, a Potential Apoptosis Imaging Agent, as Determined from PET/CT Scans in Healthy Volunteers