99mTc-exendin(9-39)/octreotide

Ocampo‐García, Blanca; Santos-Cuevas, Clara; Luna-Gutiérrez, Myrna; Ignacio-Álvarez, Eleazar; Pedraza-López, Martha; Manzano-Mayoral, Cesar

doi:10.1097/mnm.0000000000000736

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…To calculate Ã (r S , T D ), it is necessary to measure the source radioactivity at different time points to produce the time-radioactivity curve, followed by integration of this curve over T D . For clinical studies using AE emitting radionuclides such as 111 In (Fisher et al 2009; Vallis et al 2014), 99m Tc (Ocampo-Garcia et al 2017) and 123 I (Chin et al 2014), planar imaging, SPECT/CT, non-imaging whole body radioactivity monitoring, or tissue sampling (e.g. blood and urine) may be used to assay the source radioactivity (Siegel et al 1999).…”

Section: Dosimetric Propertiesmentioning

confidence: 99%

“…A shorter time period was used for estimating the doses from 111 In-DTPA-human epidermal growth factor ( 111 In-DTPA-hEGF) in 15 patients with EGFR positive breast cancer using whole body planar images acquired at 1, 4–6, 24 and 72 h p.i., since radiopeptides are eliminated more rapidly than mAbs (Vallis et al 2014). Whole-body images were obtained at 20 min, 2, 6, 24 h post injection of 99m Tc-EDDA/HYNIC-Tyr (3)-octreotide to estimate the radiation doses in 4 healthy individuals (Ocampo-Garcia et al 2017). The choice of collimators and scan time, as well as attenuation and scatter correction used in image reconstruction all have effects on the accuracy of image quantification (Dewaraja et al 2012; Siegel et al 1999).…”

Section: Dosimetric Propertiesmentioning

confidence: 99%

See 1 more Smart Citation

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

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Background: Auger electrons (AEs) are very low energy electrons that are emitted by radionuclides that decay by electron capture (e.g. 111 In, 67 Ga, 99m Tc, 195m Pt, 125 I and 123 I). This energy is deposited over nanometre-micrometre distances, resulting in high linear energy transfer (LET) that is potent for causing lethal damage in cancer cells. Thus, AE-emitting radiotherapeutic agents have great potential for treatment of cancer. In this review, we describe the radiobiological properties of AEs, their radiation dosimetry, radiolabelling methods, and preclinical and clinical studies that have been performed to investigate AEs for cancer treatment. Results: AEs are most lethal to cancer cells when emitted near the cell nucleus and especially when incorporated into DNA (e.g. 125 I-IUdR). AEs cause DNA damage both directly and indirectly via water radiolysis. AEs can also kill targeted cancer cells by damaging the cell membrane, and kill non-targeted cells through a cross-dose or bystander effect. The radiation dosimetry of AEs considers both organ doses and cellular doses. The Medical Internal Radiation Dose (MIRD) schema may be applied. Radiolabelling methods for complexing AE-emitters to biomolecules (antibodies and peptides) and nanoparticles include radioiodination (125 I and 123 I) or radiometal chelation (111 In, 67 Ga, 99m Tc). Cancer cells exposed in vitro to AE-emitting radiotherapeutic agents exhibit decreased clonogenic survival correlated at least in part with unrepaired DNA double-strand breaks (DSBs) detected by immunofluorescence for γH2AX, and chromosomal aberrations. Preclinical studies of AE-emitting radiotherapeutic agents have shown strong tumour growth inhibition in vivo in tumour xenograft mouse models. Minimal normal tissue toxicity was found due to the restricted toxicity of AEs mostly on tumour cells targeted by the radiotherapeutic agents. Clinical studies of AEs for cancer treatment have been limited but some encouraging results were obtained in early studies using 111 In-DTPAoctreotide and 125 I-IUdR, in which tumour remissions were achieved in several patients at administered amounts that caused low normal tissue toxicity, as well as promising improvements in the survival of glioblastoma patients with 125 I-mAb 425, with minimal normal tissue toxicity. Conclusions: Proof-of-principle for AE radiotherapy of cancer has been shown preclinically, and clinically in a limited number of studies. The recent introduction of many biologically-targeted therapies for cancer creates new opportunities to design novel AE-emitting agents for cancer treatment. Pierre Auger did not conceive of the application of AEs for targeted cancer treatment, but this is a tremendously exciting future that we and many other scientists in this field envision.

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Section: Dosimetric Propertiesmentioning

confidence: 99%

Section: Dosimetric Propertiesmentioning

confidence: 99%

Auger electrons for cancer therapy – a review

Facca

Cai

et al. 2019

EJNMMI radiopharm. chem.

266

207

View full text Add to dashboard Cite

show abstract

“…An overview of the physiological responses to exendin(9-39)NH 2 infusions in humans is shown in assess GLP-1 receptor antagonism as a therapeutic strategy in congenital hyperinsulinism owing to inactivating mutations in the ATP-sensitive K + channel in pancreatic beta cells, 10 postprandial hypoglycaemia in children after gastric surgery 11 or symptomatic post-bariatric hypoglycaemia. 12,13,84 Furthermore, radiolabelled exendin(9-39)NH 2 has the ability to bind to GLP-1 receptors in human tissues, for example, for insulinoma imaging 14,86 and the use of exendin(9-39)NH 2 as a radiopharmaceutical tracer for insulinomas seems promising.…”

Section: Measuring Exendin(9-39)nh 2 In Human Samplesmentioning

confidence: 99%

Exendin(9‐39)NH₂: Recommendations for clinical use based on a systematic literature review

Gasbjerg

Bari

Christensen

et al. 2021

Diabetes Obesity Metabolism

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Aim: To present an overview of exendin(9-39)NH 2 usage as a scientific tool in humans and provide recommendations for dosage and infusion regimes. Methods:We systematically searched the literature on exendin(9-39)NH 2 and included for review 44 clinical studies reporting use of exendin(9-39)NH 2 in humans.Results: Exendin(9-39)NH 2 binds to the orthosteric binding site of the glucagon-like peptide-1 (GLP-1) receptor with high affinity. The plasma elimination half-life of exendin(9-39)NH 2 after intravenous administration is $30 minutes, requiring $2.5 hours of constant infusion before steady-state plasma concentrations can be expected. Studies utilizing infusions with exendin(9-39)NH 2 in humans have applied varying regimens (priming with a bolus or constant infusion) and dosages (continuous infusion rate range 30-900 pmol/kg/min) with subsequent differences in effects.Administration of exendin(9-39)NH 2 in healthy individuals, patients with diabetes, obese patients, and patients who have undergone bariatric surgery significantly increases fasting and postprandial levels of glucose and glucagon, but has inconsistent effects on circulating concentrations of insulin and C-peptide, gastric emptying, appetite sensations, and food intake. Importantly, exendin(9-39)NH 2 induces secretion of all L cell products (ie, in addition to GLP-1, also peptide YY, glucagon-like peptide-2, oxyntomodulin, and glicentin) complicating use of exendin(9-39)NH 2 as a tool to study the isolated effect of GLP-1.Conclusions: Exendin(9-39)NH 2 is selective for the GLP-1 receptor, with numerous and complex whole-body effects. To obtain GLP-1 receptor blockade in humans, we recommend an initial high-dose infusion, followed by a continuous infusion rate aiming at a ratio of exendin(9-39)NH 2 to GLP-1 of 2000:1. Highlights• Exendin(9-39)NH 2 is a competitive antagonist of the human GLP-1 receptor.• Exendin(9-39)NH 2 has been used as a tool to delineate human GLP-1 physiology since 1998.• Exendin(9-39)NH 2 induces secretion of GLP-1 and other L cell products.• Reported effects of exendin(9-39)NH 2 on insulin levels and food intake are inconsistent.• Here, we provide recommendations for the use of exendin(9-39)NH 2 in clinical studies.

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Molecular imaging of β-cells: diabetes and beyond

Wei

Lan

Luo

et al. 2019

Advanced Drug Delivery Reviews

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Since diabetes is becoming a global epidemic, there is a great need to develop early β-cell specific diagnostic techniques for this disorder. There are two types of diabetes (i.e., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)). In T1DM, the destruction of pancreatic βcells leads to reduced insulin production or even absolute insulin deficiency, which consequently results in hyperglycemia. Actually, a central issue in the pathophysiology of all types of diabetes is the relative reduction of β-cell mass (BCM) and/or impairment of the function of individual βcells. In the past two decades, scientists have been trying to develop imaging techniques for noninvasive measurement of the viability and mass of pancreatic β-cells. Despite intense scientific efforts, only two tracers for positron emission tomography (PET) and one contrast agent for magnetic resonance (MR) imaging are currently under clinical evaluation. β-cell specific imaging probes may also allow us to precisely and specifically visualize transplanted β-cells and to improve transplantation outcomes, as transplantation of pancreatic islets has shown promise in treating T1DM. In addition, some of these probes can be applied to the preoperative detection of hidden insulinomas as well. In the present review, we primarily summarize potential tracers under development for imaging β-cells with a focus on tracers for PET, SPECT, MRI, and optical imaging. We will discuss the advantages and limitations of the various imaging probes and extend an outlook on future developments in the field. ☆ This review is part of the Advanced Drug Delivery Reviews theme issue on "Imaging and Therapy of Diabetes: State of the Art".

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99mTc-exendin(9-39)/octreotide

Abstract: All the absorbed doses were comparable to those known for most of the Tc studies. Tc-exendin(9-39)/octreotide obtained from kit formulations showed high tumor uptake in a patient with a malignant lesion, making it a promising imaging radiopharmaceutical to target GLP-1R and SSTR.

Cited by 5 publications

References 16 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Exendin(9‐39)NH₂: Recommendations for clinical use based on a systematic literature review

Molecular imaging of β-cells: diabetes and beyond

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99mTc-exendin(9-39)/octreotide

Abstract: All the absorbed doses were comparable to those known for most of the Tc studies. Tc-exendin(9-39)/octreotide obtained from kit formulations showed high tumor uptake in a patient with a malignant lesion, making it a promising imaging radiopharmaceutical to target GLP-1R and SSTR.

Cited by 5 publications

References 16 publications

Auger electrons for cancer therapy – a review

Auger electrons for cancer therapy – a review

Exendin(9‐39)NH2: Recommendations for clinical use based on a systematic literature review

Molecular imaging of β-cells: diabetes and beyond

Contact Info

Product

Resources

About

Exendin(9‐39)NH₂: Recommendations for clinical use based on a systematic literature review