Picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as potential SPECT imaging agents: syntheses and preclinical evaluation

Kadiyala, K. Ganesh; Tyagi, Tulika; Kakkar, Dipti; Chadha, Nidhi; Chuttani, Krishna; Roy, Bal Gangadhar; Thirumal, M.; Mishra, Anil K.; Datta, Anupama

doi:10.1039/c4ra13690j

Cited by 8 publications

(6 citation statements)

References 38 publications

(19 reference statements)

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“…Accurate mass (ESI): calcd for [M + Na] + (C 9 H 11 NO 3 Na + ): 204.06311; found: 204.0629. These data are in agreement with data reported for this compound.…”

Section: Methodssupporting

confidence: 93%

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A Gd^III-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

Ossadnik

Kuzin

et al. 2022

Inorg. Chem.

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The remarkably narrow central line in the electron paramagnetic resonance spectrum and the very weak zero-field splitting (ZFS) make [Gd III (NO3Pic)] ([Gd III (TPATCN)]) an attractive starting point for the development of spin labels. For retaining the narrow line of this parent complex when modifying it with a substituent enabling bioconjugation, alkyl with a somehow remote functional group as a substituent at the picolinate moiety was found to be highly suitable because ZFS stayed weak, even if the threefold axial symmetry was broken. The ZFS is so weak that hyperfine coupling and/or g-value variations noticeably determine the linewidth in Q band and higher fields when the biomolecule is protonated, which is the standard situation, and in W band and higher fields for the protonated complex in a fully deuterated surrounding. Clearly, [NDSE-{Gd III (NO3Pic)}], a spin label targeting the cysteines in a peptide, is at a limit of linewidth narrowing through ZFS minimization. The labeling reaction is highly chemoselective and, applied to a polyproline with two cysteine units, it took no more than a minute at 7 °C and pH 7.8. Subsequent disulfide scrambling is very slow and can therefore be prevented. Double electron−electron resonance and relaxationinduced dipolar modulation enhancement applied to the spin-labeled polyproline proved the spin label useful for distance determination in peptides.

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“…Accurate mass (ESI): calcd for [M + Na] + (C 9 H 11 NO 3 Na + ): 204.06311; found: 204.0629. These data are in agreement with data reported for this compound.…”

Section: Methodssupporting

confidence: 93%

“…MS [ESI obtained from the spot on a TLC plate with R f (CH 2 Cl 2 /Et 2 O, 1:1) = 0.66]: m / z = 222.2 [M( 35 Cl) + Na] + , 224.1 [M( 37 Cl) + Na] + , 421.3 [2 M( 35 Cl) + Na] + , 423.3 [M( 35 Cl) + M( 37 Cl) + Na] + . The NMR spectroscopical data are in agreement with data reported for this compound.…”

Section: Methodssupporting

confidence: 90%

A Gd^III-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

Ossadnik

Kuzin

et al. 2022

Inorg. Chem.

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“…30 The aminebis( picolinic acid) motif has been applied to the complexation of a variety of metals with a number of different amines being used to form chelates with varying properties. [31][32][33][34][35][36][37][38][39][40][41][42] The incorporation of a glycine residue into the chelate backbone provides both a carboxylic acid group that can bind strongly to Ga(III) due to a good hard acid/base match, and also a site which can be readily functionalised through application of other amino acids. 31,33 H 3 Dpaa has previously been applied to complexation of lanthanide(III) ions such as gadolinium(III) (log K GdDpaa = 10.6) 32,33 and terbium(III) (log K TbDpaa = 10.4).…”

Section: Introductionmentioning

confidence: 99%

Amino acid based gallium-68 chelators capable of radiolabeling at neutral pH

et al. 2017

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Gallium-68 (Ga) has been the subject of increasing interest for its potential in the production of radiotracers for diagnosis of diseases. In this work we report the complexation of Ga by the amino acid based tripodal chelate HDpaa, and two bifunctional derivatives, HDpaa.dab and HDpaa.ga, under a range of conditions with particular emphasis on the rapid complexation of Ga at pH 7.4. 100 μM HDpaa achieved a radiochemical yield of 95% at pH 7.4 in 5 minutes at 37 °C. The bifunctional derivatives HDpaa.ga and HDpaa.dab achieved 94% and 84% radiochemical yields, respectively, under the same conditions. The resulting Ga(iii) complexes show thermodynamic stabilities of log K = 18.53, log K = 22.08, log K = 18.36. Unfortunately, the resulting radiolabelled species do not present sufficient serum stability for in vivo application. Herein we show a flexible synthesis for bifunctional chelators based on amino acids that rapidly complex Ga under physiological conditions.

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“…Radiolabeling with 99m Tc was performed as described previously (16). DT(Ch) 2 (5.0 µmol) was dissolved in saline (PBS pH 7.4, 100 µL) in a shielded vial.…”

Section: Radiolabeling Studiesmentioning

confidence: 99%

“…99m Tc, a SPECT radiometal, has remained a cornerstone in the field of diagnostic nuclear medicine owing to it being readily available as a commercial generator. Its various favorable nuclear properties such as the half-life of 6 h, pure gamma-ray energy (E = 140 keV), and reduced radiation burden make it ideal for imaging applications (16).…”

Section: Introductionmentioning

confidence: 99%

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

et al. 2022

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Chalcone derivatives have been successfully utilized for a range of biological applications and can cross the blood–brain barrier easily. β-amyloid-specific bis-chalcone derivative, 6,9-bis(carboxymethyl)-14-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)-3-(2-[(2-(4-[(E)-3-(4-(dimethylamino)phenyl)acryloyl]phenoxy)ethyl)amino]-2-oxoethyl)-11-oxo-3,6,9,12-tetraazatetradecanoic acid, DT(Ch)2, was analyzed using molecular modeling to explain the binding modes of the ligand with amyloid fibril and monomer followed by 99mTc-complexation in 95% yield and 98.7% efficiency. High-binding specificity of the radiocomplex was established following in vitro evaluation against 100-fold excess of DT(Ch)2. 99mTc–DT(Ch)2 exhibited <3% trans-complexation in human serum after 24 h, indicating high stability. A fast clearance rate in pharmacokinetics studies displayed a biphasic pattern with t1/2(F) = 30 min ± 0.09 and t1/2(S) = 4 h 20 min ± 0.06. In vivo single-photon emission computed tomography (SPECT) imaging in rabbits reiterated the pharmacokinetics data with initially high brain uptake followed by rapid washout. Biodistribution studies confirmed the initial brain uptake as 1.16 ± 0.02% ID/g after 2 min and the brain2min/brain30min ratio was 3.74. Radioactivity distribution in the brain was >40% in the cingulate cortex followed by >25% in the hippocampus, a distribution pattern aligned to Alzheimer’s affected brain regions. Radiocomplex also displayed rapid plasma clearance followed by hepatobolic and renal modes of excretion.

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Picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as potential SPECT imaging agents: syntheses and preclinical evaluation

Abstract: Syntheses and preclinical evaluation of picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as SPECT imaging agents.

Cited by 8 publications

References 38 publications

A Gd^III-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

A Gd^III-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

Amino acid based gallium-68 chelators capable of radiolabeling at neutral pH

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

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Picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as potential SPECT imaging agents: syntheses and preclinical evaluation

Abstract: Syntheses and preclinical evaluation of picolinic acid based acyclic bifunctional chelating agent and its methionine conjugate as SPECT imaging agents.

Cited by 8 publications

References 38 publications

A GdIII-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

A GdIII-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

Amino acid based gallium-68 chelators capable of radiolabeling at neutral pH

Bio-Evaluation of 99mTc-Labeled Homodimeric Chalcone Derivative as Amyloid-β-Targeting Probe

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A Gd^III-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization

A Gd^III-Based Spin Label at the Limits for Linewidth Reduction through Zero-Field Splitting Optimization