Website is intended for physicians
Search:
Всего найдено: 3

 

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.

 

References

1.     Panov VO, Shimanovskiy NL. The diagnostic efficacy and safety of macrocyclic gadolinium-based magnetic resonance contrast agents. Russian J Radiol. 2017; 98(3): 159-166 [In Russ].

http://doi.org/10.20862/0042-4676-2017-98-3-159-166

2.     Shimanovskiy NL, Epinetov MA, Melnikov MYa. Molecular and nanopharmacology. Moscow, 2009; 624 [In Russ].

3.     National guidebook on nuclear medicine. Vol.1. Ed. by Lishmanov YuB, Chernov VI. Tomsk. STT Publ. 2010; 432 [In Russ].

4.     Litvinenko IV. The possibility of SPECT-CT in the diagnosis of coronary artery stenoses. Medical Visualization. 2015; (2): 53-66 [In Russ].

5.     Narkevich BYa, Ryzhkov AD, Komanovskaya DA et al. Estimation of radiation risks in SPECT/CT of skeletal bones. Medical Physics. 2019; 3 (83): 66-74 [In Russ].

6.     Madru R, Kjellman P, Olsson F et al. 99mTc-labeled superparamagnetic iron oxide nanoparticles for multimodality SPECT/MRI of sentinel lymph nodes. J Nucl Med. 2012; 53(3): 459-463.

http://doi.org/10.2967/jnumed.111.092437

7.     Onoprienko AV, Kostenikov NA, Velichko OB, et al. Use of Fused Images Combining Contrast-Enhanced MRI and 99mTc-MIBI SPECT in Diagnosis of Recidive Gliomas. Medical Visualization. 2004; (5): 38-46 [In Russ].

8.     Onoprienko A.V., Velichko O.B., Minin S.M. et al. Imaging of a Successful Medical Treatment of a Multiforme Glioblastoma by Means of Combination of Contrast-enhanced MRI and SPECT with 99mTc-Technetril. Medical Visualization. 2006; (2); 99-103 [In Russ].

9.     Ussov WYu, Belyanin ML, Bezlepkin Al et al. Magnetic Resonance Imaging of Brain Involvement in Dogs Using Paramagnetic Contrast Enhancement with Mn(II)-DCTA. Bull.Exp.Biol.Med. 2016; 161: 715-718.

http://doi.org/10.1007/s10517-016-3492-1

10.   Belyanin ML, Fedoushchak TA, Filimonov VD et al. Solid-nanophase synthesis and evaluation of manganese (II) complex with diethylentriaminpentaacetic acid as contrast agent for magnetic resonance imaging. Siberian medical journal (Tomsk). 2008; 23(2): 33-36 [In Russ].

11.   Zevatskiy YuE, Samoilov DV. Empiric method of quantification of influence of dissolvent on dissociation constants of carbonic acids. Zhurnal organicheskoi chimii. 2008; 44(1): 59-68 [In Russ].

12.   Kaviani S, Shahab S, Sheikhi M, Ahmadianarog M. DFT study on the selective complexation of meso-2,3-dimercaptosuccinic acid with toxic metal ions (Cd2+, Hg2+ and Pb2+) for pharmaceutical and biological applications. Journal o f Molecular Structure. 2019; (1176): 901-907.

13.   Mironov AN. Guidelines for conducting preclinical research of drugs. M. Grit and К Publ.house. 2012; 944 [In Russ].

14.   Rossotti F, Rossotti X. Determination of stability constants and other equilibrium constants in solutions. M. Mir Publ.house. 1965; 564 [In Russ].

15.   Medixant. RadiAnt DICOM Viewer [Software]. Version 2020.1. Mar 9, 2020.

URL: https://www.radiantviewer.com

16.   Ehman EC, Johnson GB, Villanueva-Meyer JE et al. PET/MRI: Where might it replace PET/CT? J Magn Reson Imaging. 2017; 46(5): 1247-1262.

http://doi.org/10.1002/jmri.25711

17.   Hochhegger B, Alves GR, Irion KL et al. PET/CT imaging in lung cancer: indications and findings. J.Bras.Pneumol. 2015; 41 (3): 264-274.

http://doi.org/10.1590/S1806-37132015000004479

18.   Ansheles AA., Sergienko VB. Interpretation of myocardial perfusion SPECT with attenuation correction. Russian Journal of Radiology. 2020; 101(1): 6-18 [In Russ].

http://doi.org/10.20862/0042-4676-2020-101-1-6-18

19.   Ussov WYu., Sinitsyn VE., Obradovich V. et al. Patterns of cerebral blood flow reactivity in adenosine stress­test in patients with carotid stenosis, evaluated with MRI and 99mTc-HMPAO SPECT brain study. Russian Journal of Radiology.2000; 81 (6): 4-9 [In Russ].

20.   Berry DJ, Torres Martin de Rosales R, Charoenphun P, Blower PJ. Dithiocarbamate complexes as radiopharmaceuticals for medical imaging. Mini Rev Med Chem. 2012; 12(12): 1174-1183.

http://doi.org/10.2174/138955712802762112

21.   Burilova EA, Ziyatdinova AB, Zyavkina Yul, Amirov RR. Influence of waterso;uble polymers on the formation of Manganese(II) complexomated in solutions. I Complexes with EDTA. Research proceedings of the Kazan University. Natural Sceinces. 2013; 155(2); 10-25 [In Russ].

22.   Belyanin ML, Prvulovich M, Karpova GV et al. Synthesis and evaluation of mangapentetate as paramagnetic contrast agent for magnetic resonance imaging. Diagnostic and Interventional Radiology. 2008; 2(1): 75-86 [In Russ].

23.   Meerovich IG, Gulyaev MV, Meerovich GA et al. Study of contrast agents based on phthalocyanin derivatives for magnetic resonance imaging. Russian chemical journal. 2013. 57(2): 110-114 [In Russ].

24.   Ussov WYu, Belyanin ML, Kodina GE et al. Magnetic resonance imaging of myocardium with paramagnetic contrast enhancement with Mn-methoxyisobutylisonitrile (Mn-MIBI) in an experiment. Medical visualization. 2016; (1): 31-38 [In Russ].

25.   Ussov VYu, Bezlepkin Al, Kovalenko AYu et al. Preclinical study of paramagnetic contrast enhancement with Mn(II)-dimercaptosuccinate complex in magnetic resonance imaging of primary tumor and metastatic spread of breast cancer. Diagnostic Radiology and Radiation Therapy. 2020; (1 (11)): 70-77 [In Russ].

http://doi.org/10.22328/2079-5343-2020-11-1-70-77

26.   Ussov VYu, Belyanin ML, Filimonov VD et al. Theoretical basis and experimental study of the Mn(II) complex with hexamethylpropylenaminoxim as a paramagnetic contrast agent for visualization of malignant tumors. Diagnostic Radiology and Radiation Therapy. 2019; (2 (10)): 42-49 [In Russ].

http://doi.org/10.22328/2079-5343-2019-10-2-42-49

27.   Serebrennikov W. Chemistry of rare earth elements (scandium, yttrium, lanthanides). Tomsk. TSU Publ. House. 1959; 531 [In Russ].

28.   Batyreva VA, Kozik W, Serebrennikov W, Yakunina GM. Synthesis of compounds of rare earth elements. Tomsk. TSU Publ. House. 1983; 144 [In Russ].

29.   Ussov VYu, Belyanin ML, Bezlepkin Al etal. Evaluation of Manganese-trans-1,2-Diaminocyclohexane-N,N,N’,N’-tetraacetate Complex (Cyclomang) as Paramagnetic Contrast Agent for Magnetic Resonance Imaging. Eksperimentalnaya i klinicheskaya farmakologiya. 2013; 76(10): 32-38 [In Russ].


Abstract:

The aim of the study was to assess the potential of nuclear imaging for long-term results assessment in myocardial infarction (MI) surgical treatment. 35 patients were included in the study: the main group (n = 15) of patients underwent bypass surgery in 3-4 weeks after MI, and the control group (n = 20) with conventional conservative MI treatment. Radionuclide angiopulmonography and radionuclide ECG-synchronized ventriculography was performed in all the patients in 1 month, 6 months, and 12 months after MI.

Scintigraphic markers of post-operative complications were the following: (1) prolongation of minimal pulmonary circulation time 1 month after operation followed by (2) right chamber passage prolongation and (3) ejection fraction decrease. Stability of the mentioned parameters can serve as a predictor of smooth postoperative course. Feebleness of pulmonary circulation occurs earlier that the ejection fraction decrease, so it can be mentioned among the earliest symptoms of heart failure in patients with MI.

 

Reference 

 

1.     Гиляревский С.Р., Орлов В.А., ГвинджилияТ.В. Коррекция постинфарктного ремоделирования сердца ингибиторами ангиотензинпревращающего фермента.  Кардиология. 1993; 12: 37-47.

 

2.     Mazzotta G., Vecchio С. Angiotensin converting enzyme inhibitors during acute phase ofmyocardial infarction.  G. Ital.  Cardiol.  1994;24 (1): 59-70.

 

3.     McKay R.G., Pfeffer M.A., Pasternak R.C. et al. Left ventricular remodelling after myocardial infarction: a corollary to infarct expansion. Circulation. 1986; 74: 693-702.

 

4.     Claes M.J., Vrints C.J.,  Bosmans J.  et al.Corinary flow reserve during coronary angioplasty in patients with a recent myocardial infarction: relation to stenosis and myocardial viability.J. Am. Coll. Card. 1996; 28: 1712-1719.

 

5.     Gersh B.J., Chesebro J.H., Braunwald E. et al.Coronary artery bypass  graft surgery afterthrombolytic therapy in the Thrombolysis inMyocardial Infarction Trial, Phase II (TIMI II).J. Am. Coll. Card. 1995; 25 (2): 395-402.

 

6.     Van`t Hof A.W.J., Liem A., Suryapranata H. etal.  Clinical presentation  and  outcome  of patients with early,  intermediate  and  late reperfusion  therapy by  primary  coronary angioplasty for acute myocardial infarction. Eur. Heart. J. 1998; 19: 118-123.

 

7.     Goldberg R.J., Gore J.M., Alpert J.S. et al. Cardiogenic  shock after acute  myocardial infarction:  incidence and mortality from a community-wide perspective,  1975 to 1988. N. Engl.J. Med. 1991; 325: 1117-1122.

 

8.     Touboul P., Andre-Fouet X., Leizoroviczt A. et al. Risk stratification after myocardial infarction. Eur. Heart. J. 1997; 18: 99-107.

 

9.     Taylor S.H. Congestive heart failure. Towards a comprehensive  treatment.  Eur.  Heart. J. 1996; 17 (B): 43-56.

 

10.   Матвеева Г.К. Артериальное давление в легочной артерии у больных ИБС, перенесших крупноочаговый и трансмуральный инфаркт миокарда, и его прогностическое значение. Aвтореф. дис. канд. мед. наук. М. 1988; 25.

11.   Hakim T.S., Michel R.P. et al. Site of pulmonary hypoxic vasoconstriction studied with arterial and venous occlusion. / Appl. Physiol. 1983; 54 (5): 1298-1302.

 

Abstract:

Background: according to the international registry ICOPER, right ventricular (RV) dysfunction is the most significant predictor of mortality in patients with pulmonary embolism (PE). Diagnosis of PE should include not only verification of thrombus in branches of pulmonary arteries, but also estimation of RV contractile function.

Aim: was to identify the most informative indicators of Gated Blood Pool SPECT (GBPS) for estimation of RV function in patients with PE.

Methods: 52 patients were included in the study Main group (n=37) included patients with PE; comparison group (n=15) included patients suffering from coronary heart disease (NYHA I-II). All patients received ventilation-perfusion lung scintigraphy, gated blood pool single photon emission computer tomography (GBPS), and estimation of plasma levels of endothelin-1, stable nitric oxide (NO) metabolites, and 6-keto-PG F1a.

Results: in patients with PE, RV end-systolic volume, stroke volume, ejection fraction, peak ejection rate, peak filling rate, and mean filling rate were significantly lower in comparison with patients without PE. In patients with PE volume from 3 to 7 bronchopulmonary segments, we have not found any correlations between PE volume and functional status of the right ventricle. In patients with PE, levels of endothelin-1, 6-keto-PG F1a, and stable NO metabolites were increased in comparison with patients without PE.

Conclusion: GBPS allows to verify RV dysfunction in patients without massive PE and severe pulmonary hypertension. Dissociation between volume of PE and the degree of RV dysfunction may be caused by humoral vasoactive factors disbalance. 

 

Reference

1.     Torbicki A., Perrier A., Konstantinides S., et al. ESC Committee for Practice Guidelines (CPG). Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur. Heart J. 2008; 29 (18): 2276-2315.

2.     Anderson F.A. Jr., Spencer F.A. Risk factors for venous thromboembolism. Circulation. 2003; 107: 9-16.

3.     Heit J.A. The epidemiology of venous thromboembolism in the community: implications for prevention and management. J. Thromb Thrombolysis. 2006; 21: 23-29.

4.     White R.H. The Epidemiology of Venous Thromboembolism. Circulation. 2003; 107: 1-4.

5.     Golghaber S.Z. Echocardiography in the Management of Pulmonary Embolysm. Ann. Intern. Med. 2002; 136 (99): 691-700.

6.     Haddad F., Hunt S.A., Rosenthal D.N. et al. Right ventricular function in cardiovascular disease, part I: Anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation. 2008; 117 (11): 1436-48.

7.     MacNee W. Pathophysiology of cor pulmonale in chronic obstructive pulmonary disease: part one. Am. J. Respi. Crit. Care Med. 1994; 150: 833-852.

8.     Zavadovskij K.V., Pan'kova A.N., Krivonogov N.G. i dr. Radionuklidnaja diagnostika trombojembolii legochnoj arterii: vizualizacii perfuzii i ventiljacii legkih, ocenka sokratimosti pravogo zheludochka [Radionuclide diagnosis of pulmonary embolism: perfusion and ventilation, assessment of right ventricular contractility]. Sibirskij medicinskij zhurnal. 2011; 26(2), vypusk 1:14-21 [In Russ].

9.     Petri A., Sjebin K. Nagljadnaja statistika v medicine. Per. s angl. V.P. Leonova. M.: GJeOTAR-MED. 2003; 144 s.: il. (Serija «Jekzamen na otlichno») [In Russ].

10.   Mansencal N., Joseph T., Vieillard-Baron A., et al. Diagnosis of right ventricular dysfunction in acute pulmonary embolism using helical computed tomography. Am. J. Cardiol. 2005; 95 (10): 1260-1263.

11.   Contractor S., Maldjian P.D., Sharma V.K. Role of helical CT in detecting right ventricular dysfunction secondary to acute pulmonary embolism. J. Comput. Assist. Tomogr. 2002;

ANGIOLOGIA.ru (АНГИОЛОГИЯ.ру) - портал о диагностике и лечении заболеваний сосудистой системы