Trans-1.2-diaminocyclohexan-N,N,N’,N’-tetraacetic acid (DCTA) as multimodal chelator for mri and single-photon emission imaging using complexes with Mn (Cyclomang) and 99mTс (Cyclotech)

DOI: https://doi.org/10.25512/DIR.2020.14.3.10

For quoting:
Ussov W.Yu., Belyanin M.L., Churin A.A., Bezlepkin A.I., Borodin O.Yu., Zorkaltsev M.A., Lishmanov Yu.B., Udut V.V., Filimonov V.D., Shimanovskiy N.L. "Trans-1.2-diaminocyclohexan-N,N,N’,N’-tetraacetic acid (DCTA) as multimodal chelator for mri and single-photon emission imaging using complexes with Mn (Cyclomang) and 99mTс (Cyclotech)". Journal Diagnostic & interventional radiology. 2020; 14(3); 91-100.

authors:

Ussov W.Yu.

Belyanin M.L.

Churin A.A.

Bezlepkin A.I.

Borodin O.Yu.

Zorkaltsev M.A.

Lishmanov Yu.B.

Udut V.V.

Filimonov V.D.

Shimanovskiy N.L.

keywords:

trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (DCTA)

Mn-DCTA

Cyclomang

99mTc–DCTA

Cyclotech

MRI

paramagnetic contrast enhancement

SPECT

SPECT/MRI

Abstract:

Aim: was to make preclinical and imaging tests of the trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (DCTA) complex as a universal contrast agent for MRI and single-photon emission imaging, with Mn (Cyclomang) and ^99mTc- (Cyclotech), respectively.

Material and Methods: the complex of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (DCTA) was synthesized at the department of organic chemistry of National Research Tomsk Polytechnic university, using the original technology in the nanopowder phase using manganese (II) carbonate, or generator eluate ^99mTc, and NaH₂DCTA, resulting in a 0.5 M solution of Мn-DCTA or ^99mTc-DCTA. LD50 values were determined in experiments on laboratory mice. A visualization study was performed in 4 cats and 3 dogs with malignant neoplasms of chest organs and in one dog with a tumor of the left pontocerebellar angle. All of them underwent consecutively MRI with contrast enhancement with Mn-DCTA and SPECT - with ^99mTc-DCTA.

Results: for Cyclotech LD50 >18/ml/kg, for 0.5 M Mn-DCTA (Cyclomang) solution, the LD50 index significantly exceeds 16.9 ml/kg BW. Changes in the content of manganese in the blood plasma of rats when they were administered Mn-DCTA, did not occur. LD50 values allow us to assign the drug in accordance with Russian regulation GOST 12.1.007-76. to group 4 (low-hazard substances). In both cases, in the range of physiological pH, the thermodynamic stability constant is >19.3. In studies in animals with MRI, the enhancement index of T1-weighted spin-echo image of the tumor in all cases exceeded 1.7 (mean 1.82±0.10). When calculating the «tumor/back-ground» index for ^99mTc-DCTA, it was 2.6-7.3 (mean 4.12±1.05).

Conclusion: DCTA complexes with manganese (II) - for enhancement in MRI and with ^99mTc- for SPECT- have very close pharmacokinetic properties, are non-toxic, do not dissociate in physiological environments and can be further used for contrast enhancement in multimodal MRI-SPECT studies. Chelate agents of the ^99mTc with thermodynamic stability constants over 16 may be employed in the nearest future as important source for the development of paramagnetic contrast agents binding Mn.

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