Dataset Information

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

ABSTRACT:

Objective

Metastasis 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.

Methods

⁶⁸Ga 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.

Results

The 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.

SUBMITTER: Jaswal AP

PROVIDER: S-EPMC5465288 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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

Jaswal Ambika P AP Meena Virendra K VK Prakash Surbhi S Pandey Ankita A Singh Baljinder B Mishra Anil K AK Hazari Puja P PP

Frontiers in medicine 20170609

<h4>Objective</h4>Metastasis 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 [<sup>68</sup>Ga]-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 [<sup>188</sup>Re]-CDTMP for bone pain palliati ...[more]

PMID: 28649566

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