A DOTA based bisphosphonate with an albumin binding moiety for delayed body clearance for bone targeting
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
27560354
DOI
10.1016/j.nucmedbio.2016.07.009
PII: S0969-8051(16)30135-4
Knihovny.cz E-zdroje
- Klíčová slova
- (68)Ga, Albumin-binder, Bisphosphonate, Bone metastases, DOTA, PET,
- MeSH
- adsorpce MeSH
- bisfosfonáty chemie metabolismus farmakokinetika MeSH
- heterocyklické sloučeniny monocyklické chemie MeSH
- hydroxyapatit chemie MeSH
- kosti a kostní tkáň diagnostické zobrazování metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- potkani Wistar MeSH
- pozitronová emisní tomografie MeSH
- radioizotopy galia MeSH
- sérový albumin metabolismus MeSH
- tkáňová distribuce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid MeSH Prohlížeč
- bisfosfonáty MeSH
- heterocyklické sloučeniny monocyklické MeSH
- hydroxyapatit MeSH
- radioizotopy galia MeSH
- sérový albumin MeSH
Radiolabeled bisphosphonates are commonly used in the diagnosis and therapy of bone metastases. Blood clearance of bisphosphonates is usually fast and only 30%-50% of the injected activity is retained in the skeleton, while most of the activity is excreted by the urinary tract. A longer blood circulation may enhance accumulation of bisphosphonate compounds in bone metastases. Therefore, a chemically modified macrocyclic bisphosphonate derivative with an additional human albumin binding entity was synthesized and pharmacokinetics of its complex was evaluated. The DOTA-bisphosphonate conjugate BPAMD was compared against the novel DOTAGA-derived albumin-binding bisphosphonate DOTAGA(428-d-Lys)MBP (L1). The ligands were labeled with 68Ga(III) and were evaluated in in vitro binding studies to hydroxyapatite (HA) as well as to human serum albumin. The compounds were finally compared in in vivo PET and ex vivo organ distribution studies in small animals over 6h. Binding studies revealed a consistent affinity of both bisphosphonate tracers to HA. Small animal PET and ex vivo organ distribution studies showed longer blood retention of [68Ga]L1. [68Ga]BPAMD is initially more efficiently bound to the bone but skeletal accumulation of the modified compound and [68Ga]BPAMD equalized at 6h p.i. Ratios of femur epiphyseal plate to ordinary bone showed to be more favorable for [68Ga]L1 than for [68Ga]BPAMD due to the longer circulation time of the new tracer. Thus, the chemical modification of BPAMD toward an albumin-binding bisphosphonate, L1, resulted in a novel PET tracer which conserves advantages of both functional groups within one and the same molecule. The properties of this new diagnostic tracer are expected to be preserved in 177Lu therapeutic agent with the same ligand (a theranostic pair).
Department of Inorganic Chemistry Charles University Prague Czech Republic
Department of Nuclear Medicine University Hospital Mainz Germany
Institute of Nuclear Chemistry Johannes Gutenberg University Mainz Germany
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