Investigation of 68Ga-tripolyphosphate as a potential bone-scanning agent

Goulet, Richard T.; Shysh, A.; Noujaim, A.A.; Lentle, Brian C.

doi:10.1016/0020-708x(75)90116-7

Cited by 10 publications

(4 citation statements)

References 6 publications

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“…Investigations of 68 Ga-labeled compounds for bone imaging were previously described in the 1970s [25,26]. In these reports, gallium was In this study, 67 Ga-DOTA did not bind HA in vitro and did not accumulate in bone in vivo at all (Fig.…”

Section: Discussionmentioning

confidence: 66%

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: 66%

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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“…A review of published reports of bone-seeking agents such as [68Ga]-labeled citrate (22), [68Ga]-labeled tripolyphosphate (23), [ 18 F] and [ 68 Ga]-labeled ethylenediamine tetramethylene phosphonate (24–27) bone-seeking agents did not validate sufficient potential for their clinical application.…”

Section: Discussionmentioning

confidence: 99%

“…68 Ga possess a half-life of 68 min; positron emission fraction of β + 89%; and E + β max 1.9 MeV is a positron-emitting nuclide reported with a remarkable clinical imaging potential, as the radionuclide can be easily obtained on-site from 68 Ge/ 68 Ga generators ( 19 – 21 ). A review of published reports of bone-seeking agents such as [68Ga]-labeled citrate ( 22 ), [68Ga]-labeled tripolyphosphate ( 23 ), [ 18 F] and [ 68 Ga]-labeled ethylenediamine tetramethylene phosphonate ( 24 – 27 ) bone-seeking agents did not validate sufficient potential for their clinical application.…”

Section: Discussionmentioning

confidence: 99%

[68Ga]/[188Re] Complexed [CDTMP] Trans-1,2-Cyclohexyldinitrilotetraphosphonic Acid As a Theranostic Agent for Skeletal Metastases

et al. 2017

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ObjectiveMetastasis of the osseous tissue is one of the frequent and severe aggravations as a result of several neoplastic conditions, such as metabolic disorders, infections, and cancer. The objective of this study was to evaluate the pertinence of [68Ga]-trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid (CDTMP) as a potential bone imaging agent for positron emission tomography (PET) applications as well as to assess [188Re]-CDTMP for bone pain palliation in metastatic skeletal disorders.Methods68Ga complex of CDTMP was prepared at 80°C at pH 3.5, and 188Re complex of CDTMP was prepared at room temperature. [68Ga]-CDTMP complex was investigated as PET tracer while the therapeutic efficacy was assessed for [188Re]-CDTMP. Labeling efficiency, biodistribution, myelotoxicity, and imaging studies were carried out for the complexes synthesized. Both PET and MicroPET imaging studies were performed for [68Ga]-CDTMP whereas SPECT acquisitions were acquired for [188Re]-CDTMP. Data were analyzed semiquantitatively for all the scintigraphic scans obtained.ResultsThe radiolabeling efficiency was observed to be >70% for [68Ga]-CDTMP. High bone uptake of [68Ga]-CDTMP as compared to contralateral tissue was found in PET imaging in Balb/C mice and New Zealand rabbit; the similar result for bone uptake was correlated in the biodistribution study of the compound in BALB/c mice at different time intervals. Biodistribution experiments carried out in mice showed maximum uptake of 6.12 ± 1.22%ID/g at 45 min postinjection. For [188Re]-CDTMP, total skeletal uptake was 8.12 ± 1.11%ID/g observed at 1 h postinjection from biodistribution data. High renal uptake confirms renal route of excretion. A good hydroxyapatite binding too was seen for both the complexes. No evidence of destruction or adverse functioning of vital organs was observed for the 188Re complex.Conclusion[68Ga]-CDTMP complex can be used as a promising PET bone imaging agent and [188Re]-CDTMP as a surrogate moiety for therapeutic application. Owing to the short half-life of 68Ga (68 min), cyclotron-independent radiopharmacy, fast clearance, and rapid renal excretion as evidenced in preclinical animal models. Very low myelotoxicity and highly selective bone uptake prove the potential of [188Re]-CDTMP for therapeutic application.

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“…Investigations of 68 Ga-labeled compounds for bone imaging were previously reported in the 1970s [33, 34]. In these reports, gallium was labeled with tripolyphosphate or ethylenediamine tetramethylene phosphonate (EDTMP) or diethylenetriamine pentamethylene phosphonate (DTPMP).…”

Section: Radiogallium-labeled Compounds As Bone Imaging Agents Formentioning

confidence: 99%

Advances in Drug Design of Radiometal-Based Imaging Agents for Bone Disorders

Ogawa

Saji

2011

International Journal of Molecular Imaging

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Nuclear medicine bone imaging has been the optimum diagnosis for the detection of bone disorders because the lesion could be detectable before the appearance of symptomatic and radiographic changes. Over the past three decades, 99mTc-MDP and 99mTc-HMDP have been used as bone scintigraphic agents because of their superior biodistribution characteristics, although they are far from optimal from a chemical and pharmaceutical point of view. Recently, a more logical drug design has been proposed as a concept of bifunctional radiopharmaceuticals in which the carrier molecules (bisphosphonates) and radiometal chelating groups are separated within a molecule, specifically, 99mTc-mononuclear complex-conjugated bisphosphonate. Some of the 99mTc-mononuclear complex-conjugated bisphosphonate compounds showed superior biodistribution in preclinical studies. Moreover, the drug design concept could be applied to 68Ga PET bone imaging agents. These studies would provide useful information for the development of radiometal-based imaging and therapeutic agents for bone disorders such as bone metastases.

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Investigation of 68Ga-tripolyphosphate as a potential bone-scanning agent

Cited by 10 publications

References 6 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

[68Ga]/[188Re] Complexed [CDTMP] Trans-1,2-Cyclohexyldinitrilotetraphosphonic Acid As a Theranostic Agent for Skeletal Metastases

Advances in Drug Design of Radiometal-Based Imaging Agents for Bone Disorders

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