Bone-Seeking Probes for Optical and Magnetic Resonance Imaging

Kubíček, Vojtěch; Lukeš, Ivan

doi:10.4155/fmc.09.162

Cited by 20 publications

(18 citation statements)

References 54 publications

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“…Generally, bone targeting is mostly realized via attachment of a germinal bis(phosphonate) moiety to a molecule to be delivered to bone (8)(9)(10)(11). Generally, bone targeting is mostly realized via attachment of a germinal bis(phosphonate) moiety to a molecule to be delivered to bone (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Gallium(III) complexes of NOTA‐bis (phosphonate) conjugates as PET radiotracers for bone imaging

Holub

Meckel²,

Kubíček

et al. 2014

Contrast Media & Molecular

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Ligands with geminal bis(phosphonic acid) appended to 1,4,7-triazacyclonone-1,4-diacetic acid fragment through acetamide (NOTAM(BP) ) or methylenephosphinate (NO2AP(BP) ) spacers designed for (68) Ga were prepared. Ga(III) complexation is much faster for ligand with methylenephosphinate spacer than that with acetamide one, in both chemical (high reactant concentrations) and radiolabeling studies with no-carrier-added (68) Ga. For both ligands, formation of Ga(III) complex was slower than that with NOTA owing to the strong out-of-cage binding of bis(phosphonate) group. Radiolabeling was efficient and fast only above 60 °C and in a narrow acidity region (pH ~3). At higher temperature, hydrolysis of amide bond of the carboxamide-bis(phosphonate) conjugate was observed during complexation reaction leading to Ga-NOTA complex. In vitro sorption studies confirmed effective binding of the (68) Ga complexes to hydroxyapatite being comparable with that found for common bis(phosphonate) drugs such as pamindronate. Selective bone uptake was confirmed in healthy rats by biodistribution studies ex vivo and by positron emission tomography imaging in vivo. Bone uptake was very high, with SUV (standardized uptake value) of 6.19 ± 1.27 for [(68) Ga]NO2AP(BP) ) at 60 min p.i., which is superior to uptake of (68) Ga-DOTA-based bis(phosphonates) and [(18) F]NaF reported earlier (SUV of 4.63 ± 0.38 and SUV of 4.87 ± 0.32 for [(68) Ga]DO3AP(BP) and [(18) F]NaF, respectively, at 60 min p.i.). Coincidently, accumulation in soft tissue is generally low (e.g. for kidneys SUV of 0.26 ± 0.09 for [(68) Ga]NO2AP(BP) at 60 min p.i.), revealing the new (68) Ga complexes as ideal tracers for noninvasive, fast and quantitative imaging of calcified tissue and for metastatic lesions using PET or PET/CT.

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Section: Introductionmentioning

confidence: 99%

Gallium(III) complexes of NOTA‐bis (phosphonate) conjugates as PET radiotracers for bone imaging

Holub

Meckel²,

Kubíček

et al. 2014

Contrast Media & Molecular

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“…Their high affinity to hydroxyapatite, which is the main inorganic component of bone tissue, provides extensive medical applications in the treatment of osteoporosis and other diseases of calcified tissues 4. The anchoring of BPs on the surface of titanium dioxide,5–7 iron oxides8–11 and many other inorganic materials has been employed in a broad range of academic and industrial applications 2,3,12,13. An important class of BPs are those that bear an amine group in the side chain.…”

Section: Introductionmentioning

confidence: 99%

Aminoalkyl‐1,1‐bis(phosphinic acids): Stability, Acid–Base, and Coordination Properties

et al. 2014

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Four geminal bis(phosphinic acids), namely, aminomethylbis(H‐phosphinic acid) (H2L1) and 4‐aminobutyl‐1‐hydroxy‐1,1‐bis(R‐phosphinic acid) with R = H (H2L2), Me (H2L3) and CH2CH2COOH (H4L4), were studied. Their acid–base properties and coordination ability towards Cu2+, Ni2+ and Zn2+ ions were studied by potentiometry, UV/Vis spectroscopy and NMR spectroscopy. The amine group in H2L1 has a lower protonation constant (log Ka = 6.79) than those found for other studied bisphosphinates (log Ka = 10.75–11.05) with distant amine groups. The structure of [Ca(H2L2‐O,O′)(HL2‐O,O′)]Cl revealed an octahedral arrangement of the metal coordination sphere and a linear polymeric structure, which forms through eight‐membered Ca(–O–P–O–)2Ca rings. The structure of [Cu(HL3‐O,O′)2(H2O)]·5H2O shows two chelating bisphosphinate groups in an equatorial O4 environment. The structure of [Cu(H0.5L3‐O,O′)(NO3)0.5]·2.25H2O shows two different coordination environments, one is an elongated tetragonal pyramid, and the other is a trigonal bipyramid with a bidentate nitrate ion.

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“…A common feature of most bone-seeking agents is a strong affinity for metal cations. 1–3 For example, commercially available fluorescent dyes with Ca 2+ chelation ability have been used for several decades to stain samples of bone and teeth. 4–9 Typically, the dyes emit visible wavelengths, which is a limitation for in vivo studies due to poor penetration of visible light through skin and tissue.…”

Section: Introductionmentioning

confidence: 99%

“…27 In this report, we describe the preparation and evaluation of new squaraine rotaxane probes that are decorated with multiple iminodiacetate groups as the bone targeting units. Iminodiacetates have inherently lower bone affinity than bisphosphonates (Ca 2+ association constants) 1 but we reasoned that probe association could be enhanced by creating multivalent versions. In addition to commercial visible dyes with two iminodiacetate groups, such as the green emitting Calcein, there are previous reports of bone-seeking molecular probes with three or four iminodiacetate groups, 28, 29 but none of these literature compounds were tested in vivo.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Imaging of Bone Using a Deep-Red Fluorescent Molecular Probe Bearing Multiple Iminodiacetate Groups

2013

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Deep-red fluorescent molecular probes are described that have dendritic molecular architecture with a squaraine rotaxane core scaffold and multiple peripheral iminodiacetate groups as the bone targeting units. Iminodiacetates have inherently lower bone affinity than bisphosphonates and a major goal of the study was to determine how many appended iminodiacetate groups are required for effective deep-red fluorescence imaging of bone in living rodents. A series of in vitro and in vivo imaging studies showed that a tetra(iminodiacetate) probe stains bones much more strongly than an analogous bis(iminodiacetate) probe. In addition, a control tetra(iminodiapropionate) probe exhibited no bone targeting ability. The tetra(iminodiacetate) probe targeted the same regions of high bone turnover as the near-infrared bisphosphonate probe OsteoSense®750. Longitudinal studies showed that the fluorescence image signal from living mice treated with the tetra(iminodiacetate) probe was much more stable over 19 days than the signal from OsteoSense®750. The narrow emission band of the tetra(iminodiacetate) probe makes it very attractive for inclusion in multiplex imaging protocols that employ a mixture of multiple fluorescent probes in preclinical studies of bone growth or in fluorescence guided surgery. The results also suggest that molecules or nanoparticles bearing multivalent iminodiacetate groups have promise as bone targeting agents with tunable properties for various pharmaceutical applications.

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Bone-Seeking Probes for Optical and Magnetic Resonance Imaging

Cited by 20 publications

References 54 publications

Gallium(III) complexes of NOTA‐bis (phosphonate) conjugates as PET radiotracers for bone imaging

Gallium(III) complexes of NOTA‐bis (phosphonate) conjugates as PET radiotracers for bone imaging

Aminoalkyl‐1,1‐bis(phosphinic acids): Stability, Acid–Base, and Coordination Properties

In Vivo Imaging of Bone Using a Deep-Red Fluorescent Molecular Probe Bearing Multiple Iminodiacetate Groups

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