Pre vivo, ex vivo and in vivo evaluations of [68Ga]-EDTMP

Mitterhauser, Markus; Toegel, Stefan; Wadsak, Wolfgang; Lanzenberger, Rupert; Mien, Leonhard‐Key; Kuntner, Claudia; Wanek, Thomas; Eidherr, Harald; Ettlinger, Dagmar E.; Viernstein, Helmut; Kluger, Robert; Dudczak, Robert; Kletter, Kurt

doi:10.1016/j.nucmedbio.2007.03.002

Cited by 36 publications

(23 citation statements)

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“…Recently, 68 Ga-EDTMP was re-evaluated by Mitterrhauser et al [28]. However, they stated that the advantage of 68 Ga-EDTMP over [ 18 F]-fluoride was not apparent and that the future clinical prospect of 68 Ga-EDTMP remained speculative.…”

Section: Discussionmentioning

confidence: 99%

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

Ogawa

Takai

Kanbara

et al. 2011

Nuclear Medicine and Biology

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Introduction:68 Ga is a radionuclide of great interest as a positron emitter for PET. To develop a new bone-imaging agent with radiogallium, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as a chelating site and Ga-DOTA complex-conjugated bisphosphonate, which has a high affinity for bone, was prepared and evaluated. Although we are interested in developing 68 Ga labeled bone imaging agents for PET, in these initial studies 67 Ga was used because of its longer half-life. Methods:DOTA-conjugated bisphosphonate (DOTA-Bn-SCN-HBP) was synthesized by conjugation of 2-(4-isothiocyanatebenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraac etic acid (p-SCN-Bn-DOTA) to 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (alendronate).67 Ga-DOTA-Bn-SCN-HBP was prepared by coordination with 67 Ga, and its in vitro and in vivo evaluations were performed. Ogawa et al. 4/35 Results:67 Ga-DOTA-Bn-SCN-HBP was prepared with a radiochemical purity of over 95% without purification. 67 Ga-DOTA-Bn-SCN-HBP had great affinity for hydroxyapatite in binding assay. In biodistribution experiments, 67 Ga-DOTA-Bn-SCN-HBP accumulated in bone rapidly but was hardly observed in tissues other than bone. Pretreatment of an excess amount of alendronate inhibited the bone accumulation of 67 Ga-DOTA-Bn-SCN-HBP. Conclusions:67 Ga-DOTA-Bn-SCN-HBP showed ideal biodistribution characteristics as a bone-imaging agent. These findings should provide useful information on the drug design of bone-imaging agents for PET with 68 Ga. Ogawa et al. 5/35

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Section: Discussionmentioning

confidence: 99%

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

Ogawa

Takai

Kanbara

et al. 2011

Nuclear Medicine and Biology

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“…Interestingly, experimental data on the tracer's uptake on Hap are difficult to compare for various experimental setups. A recently published study on binding of 68 Ga-EDTMP showed 4.3 ± 2.7% on 3 mg Hap after 120 min only [8]. The authors used commercially available multibone kits with 25 mg EDTMP and added 2 mL of a 0.1 M HCl direct generator eluate together with isotonic saline and kept it at ambient temperature for 30 min.…”

Section: Binding Studiesmentioning

confidence: 99%

“…Recent work [8,9] used a large amount of 25 mg EDTMP for complexing 68 Ga 3+ . Our experiments indicate that at best 1 mg of EDTMP is needed to identify 68 Ga-EDTMP bone uptake in rats (which is about > 1.5 mg/kg body weight).…”

Section: μ-Pet Measurementsmentioning

confidence: 99%

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Comparison of different phosphorus-containing ligands complexing ⁶⁸Ga for PET-imaging of bone metabolism

Fellner

Riss²,

Loktionova³

et al. 2010

Radiochimica Acta

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Ga-68 / Macrocylic ligands / Phosphonates / Complex formation / Bone metastasesSummary. 99m Tc-phosphonate structures are well established tracers for bone tumour imaging. Our objective was to investigate different 68 Ga-labelled phosphonate ligands concerning labelling kinetics, binding to hydroxyapatite and bone imaging using μ-PET. Seven macrocyclic phosphoruscontaining ligands and EDTMP were labelled in nanomolar scale with n.c.a. 68 Ga in Na-HEPES buffer at pH ∼ 4. Except for DOTP, all ligands were labelled with > 92% yield. Binding of the 68 Ga-ligand complexes on hydroxyapatite was analysed to evaluate the effect of the number of the phosphorus acid groups on adsorption parameters. Adsorption of 68 Ga-EDTMP and 68 Ga-DOTP was > 83%. For the 68 Ga-NOTA-phosphonates an increasing binding with increasing number of phosphonate groups was observed but was still lower than 68 Ga-DOTP and 68 Ga-EDTMP. μ-PET studies in vivo were performed with 68 Ga-EDTMP and 68 Ga-DOTP with Wistar rats. While 68 Ga-EDTMP-PET showed uptake on bone structures, an excess amount of the ligand (> 1.5 mg EDTMP/kg body weight) had to be used, otherwise the 68 Ga 3+ is released from the complex and forms gallium hydroxide or it is transchelated to 68 Ga-transferrin. As a result, the main focus of further phosphonate structures has to be on complex formation in high radiochemical yields with macrocyclic ligands with phosphonate groups that are not required for complexing 68 Ga.

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“…However, the production of positron emitting PET nuclides generally requires a dedicated and costly cyclotron in close proximity to the imaging facility due to the short half-lives of radionuclides. It is for this reason that radiolabeling drugs/molecular markers with PET-radiotracers are difficult to produce and image within the time frame of their decay [52]. 68 Ga is a valuable alternative to 18 F for PET imaging because it does not need an on-site cyclotron and also because of its high positron emission of 1.899 MeV [52, 53].…”

Section: Molecular Imaging Systems In Cancermentioning

confidence: 99%

Image-Guided Nanosystems for Targeted Delivery in Cancer Therapy

Iyer

Amiji

2012

CMC

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Current challenges in early detection, limitations of conventional treatment options, and the constant evolution of cancer cells with metastatic and multi-drug resistant phenotypes require novel strategies to effectively combat this deadly disease. Nanomedical technologies are evolving at a rapid pace and are poised to play a vital role in diagnostic and therapeutic interventions - the so-called “theranostics” – with potential to advance personalized medicine. In this regard, nanoparticulate delivery systems can be designed with tumor seeking characteristics by utilizing the inherent abnormalities and leaky vasculature of solid tumors or custom engineered with targeting ligands for more specific tumor drug targeting. In this review we discuss some of the recent advances made in the development of multifunctional polymeric nanosystems with an emphasis on image-guided drug and gene delivery. Multifunctional nanosystems incorporate variety of payloads (anticancer drugs and genes), imaging agents (optical probes, radio-ligands, and contrast agents), and targeting ligands (antibodies and peptides) for multi-pronged cancer intervention with potential to report therapeutic outcomes. Through advances in combinatorial polymer synthesis and high-throughput testing methods, rapid progress in novel optical/radiolabeling strategies, and the technological breakthroughs in instrumentation, such as hybrid molecular and functional imaging systems, there is tremendous future potential in clinical utility of theranostic nanosystems.

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Pre vivo, ex vivo and in vivo evaluations of [68Ga]-EDTMP

Cited by 36 publications

References 10 publications

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

Comparison of different phosphorus-containing ligands complexing ⁶⁸Ga for PET-imaging of bone metabolism

Image-Guided Nanosystems for Targeted Delivery in Cancer Therapy

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Pre vivo, ex vivo and in vivo evaluations of [68Ga]-EDTMP

Cited by 36 publications

References 10 publications

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

Preparation and evaluation of a radiogallium complex-conjugated bisphosphonate as a bone scintigraphy agent

Comparison of different phosphorus-containing ligands complexing 68Ga for PET-imaging of bone metabolism

Image-Guided Nanosystems for Targeted Delivery in Cancer Therapy

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Comparison of different phosphorus-containing ligands complexing ⁶⁸Ga for PET-imaging of bone metabolism