[ 68 Ga]/[ 188 Re] 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 [ 68 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 [ 188 Re]-CDTMP for bone pain palliation in metastatic skeletal disorders. Methods: 68 Ga complex of CDTMP was prepared at 80°C at pH 3.5, and 188 Re complex of CDTMP was prepared at room temperature. [ 68 Ga]-CDTMP complex was investigated as PET tracer while the therapeutic efficacy was assessed for [ 188 Re]-CDTMP. Labeling efficiency, biodistribution, myelotoxicity, and imaging studies were carried out for the complexes synthesized. Both PET and MicroPET imaging studies were performed for [ 68 Ga]-CDTMP whereas SPECT acquisitions were acquired for [ 188 Re]-CDTMP. Data were analyzed semiquantitatively for all the scintigraphic scans obtained. Results: The radiolabeling efficiency was observed to be > 70% for [ 68 Ga]-CDTMP. High bone uptake of [ 68 Ga]-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 [ 188 Re]-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 188 Re complex. Conclusion: [ 68 Ga]-CDTMP complex can be used as a promising PET bone imaging agent and [ 188 Re]-CDTMP as a surrogate moiety for therapeutic application. Owing to the short half-life of 68 Ga (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 [ 188 Re]-CDTMP for therapeutic application.