Imaging of Clot by 99mTc-HMPAO Labeled Platelet in Animal Model Induced Thrombosis

Document Type : Research article

Authors

1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

2 Department of Nuclear Medicine, Vali-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Neurology, School of Medicine, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

4 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

5 Radiation Application Research School, Nuclear Science and Technology Research Institute, NSTRI, Tehran, Iran.

6 Department of Pathology, Cancer Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

7 Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Abstract

99mTc-HMPAO labeled platelet (LP) imaging may integrate thrombosis imaging into routine clinical procedures. In the current study, we assessed the feasibility of the use of 99mTc-HMPAO LP for imaging of small clots in an animal model. Thrombosis was induced by application of FeCl3 solution in the distal part of the inferior vena cava (IVC) of a 6100 g anesthetized rabbit and in a male Wistar rat weighing 420 g. Twenty minutes later, 178 MBq 99mTc-HMPAO LP was injected. 99mTc-HMPAO LP preparation was done as defined and standardized in a previous report. Whole body and SPECT imaging were done 60, 90, and 120 min after tracer injection. Then, the clotted part of the vein was extracted and then its activity and pathologic evaluations were compared with the proximal part of the IVC at a similar volume.A 17 × 6 mm clot was clearly detected with both planar and SPECT imaging. The count to pixel ratio (CPR) of the clotted part of the vein was 35, 40, and 40 compared to the non-clotted vein (i.e. 19, 18, and 21) at 60, 90, and 120 min, respectively. After clot extraction, the CPR decreased to 14. The clot activity was 0.44 MBq compared to 0.01 MBq of the normal control vein. Also, clot induction was pathologically proven.99mTc-HMPAO LP preparation is logistically possible in clinical nuclear medicine and the ability of imaging small size clots encourages future trials for real clinical thrombotic scenarios.

Graphical Abstract

Imaging of Clot by 99mTc-HMPAO Labeled Platelet in Animal Model Induced Thrombosis

Keywords


(1)        Yun AJ, Lee PY and Bazar KA. Can thromboembolism be the result, rather than the inciting cause, of acute vascular events such as stroke, pulmonary embolism, mesenteric ischemia, and venous thrombosis?: a maladaptation of the prehistoric trauma response. Med. Hypotheses (2005) 64: 706-16.
(2)        Heo JH, Kim K, Yoo J, Kim YD, Nam HS and Kim EY. Computed Tomography-Based Thrombus imaging for the prediction of recanalization after reperfusion therapy in stroke. J. Stroke (2017) 19: 40-9.
(3)        Connor S and Jarosz J. Magnetic resonance imaging of cerebral venous sinus thrombosis. Clin. Radiol. (2002) 57: 449-61.
(4)        Mfoumou E, Tripette J, Blostein M and Cloutier G. Time-dependent hardening of blood clots quantitatively measured in-vivo with shear-wave ultrasound imaging in a rabbit model of venous thrombosis. Thromb. Res. (2014) 133: 265-71.
(5)        Moore RD, Rutter ED, Zapko DR, Kolade VO and Ayyoub SM. Abdominal aortic aneurysm with inferior vena cava compression in association with deep venous thrombosis. Am. J. Med. Sci. (2013) 346: 521-2.
(6)        Issar P, Chinna S and Issar SK. Evaluation of cerebral venous thrombosis by CT, MRI and MR venography. J. Assoc. Physicians India (2017) 65: 16-21.
(7)        Jain TK, Phulsunga RK, Kumar S, Sood A, Bhattacharya A and Mittal BR. Lung or liver: An imaging dilemma on Tc-99m macroaggregated albumin lung perfusion scintigraphy. Indian J. Nucl. Med. (2015) 30: 362-3.
(8)        Zhou Y, Chakraborty S and Liu S. Radiolabeled cyclic RGD peptides as radiotracers for imaging tumors and thrombosis by SPECT. Theranostics (2011) 1: 58-82.
(9)        Peters A, Lavender J, Needham S, Loutfi I, Snook D, Epenetos A, Lumley P, Keery RJ and Hogg N. Imaging thrombus with radiolabelled monoclonal antibody to platelets. Br. Med. J. (Clin Res Ed). (1986) 293: 1525-7.
(10)      Becker W, Börner W, Borst U, Kromer E and Gruner K. Tc-99m-HMPAO: A new platelet
labelling compound?. Eur. J. Nucl. Med. (1987) 13: 267-8.
(11)      Honkanen T, Jauhola S, Karppinen K, Paul R, Sakki S and Vorne M. Venous thrombosis: a controlled study on the performance of scintigraphy with 99Tcm-HMPAO-labelled platelets versus venography. Nucl. Med. Commun. (1992) 13: 88-94.
(12)      Vorne M, Honkanen T, Lantto T, Laitinen R, Karppinen K and Jauhola S. Thrombus imaging with 99mTc-HMPAO-labeled platelets and 111In-labeled monoclonal antifibrin antibodies. Acta Radiol. (1993) 34: 59-63.
(13)      Hardeman M. Platelet isolation technique and viability testing. Clinical Application of Radiolabelled Platelets, Springer (1990) 7-25.
(14)      Parvizi M, Farzanefar S, Khalaj A, Tafakhori A, Johari Daha F, Saffar H, Sadeghzadeh M, Naseri M, Ahmadzadehfar H and Abbasi M. 99mTechnetium-HMPAO labeled platelet scan in practice: preparation, quality control and biodistribution studies. (Under reviw process)
(15)      Barboza MF, Muramoto E, Herrerias R, Cruz J and Isaac MA. 99m Tc-d,l HMPAO, kit formulation and quality control. Proceedings of the 3 Brazilian Meeting on Nuclear Applications v 2; (1995) Brazil.
(16)      de Vries EF, Roca M, Jamar F, Israel O and Signore A. Guidelines for the labelling of leucocytes with 99m Tc-HMPAO. Eur. J. Nucl. Med. Mol. Imaging (2010) 37: 842-8.
(17)      Martín-Comín J, Thakur M, Piera C, Roca M and Lomeña F. Radiolabeled Blood Elements: Recent Advances in Techniques and Applications: Springer Science & Business Media; (2012).
(18)      von Bruchhausen F and Walter U. Platelets and their factors: Springer Science & Business Media; (2012).
(19)      Wang X, Smith P, HSU MY, Ogletree M and Schumacher W. Murine model of ferric chloride‐induced vena cava thrombosis: evidence for effect of potato carboxypeptidase inhibitor. J. Thromb. Haemost. (2006) 4: 403-10.
(20)      Surin W, Prakash P, Barthwal M and Dikshit M. Optimization of ferric chloride induced thrombosis model in rats: effect of anti-platelet and anti-coagulant drugs. J. Pharmacol Toxicol. Methods (2010) 61: 287-91.
(21)      Suchkova V, Baggs R and Francis C. Effect of 40-kHz ultrasound on acute thrombotic ischemia in a rabbit femoral artery thrombosis model. Circulation (2000) 101: 2296-301.
(22)      Diaz JA, Obi AT, Myers Jr DD, Wrobleski SK, Henke PK, Mackman N and Wakefield TW. Critical review of mouse models of venous thrombosis. Arterioscler. Thromb. Vasc. Biol. (2012) 32: 556-62.
(23)      Eckly A, Hechler B, Freund M, Zerr M, Cazenave JP, Lanza F, Mangin PH and Gachet C. Mechanisms underlying FeCl3‐induced arterial thrombosis. J. Thromb. Haemost. (2011) 9: 779-89.
(24)      Lin KC, Lu HI, Chen YL, Tsai TH, Chang LT, Leu S, Hsu SY, Sun CK, Chai HT, Chang HW, Chang CL, Chen HH and Yip HK. Impact of rosuvastatin treatment on reduction of thrombus burden in rat acute inferior vena cava stenosis. J. Inflamm. (2014) 11: 27.
(25)      Becker W, Borst U, Krahe T and Börner W. Tc-99m-HMPAO labelled human platelets: in-vitro and in-vivo results. Eur. J. Nucl. Med. Mol. Imaging (1989) 15: 296-301.
(26)      Vorne M, Honkanen T, Karppinen K, Röning M and Sakki S. Radiolabelling of human platelets with 99mTc‐HMPAO. Eur. J. Haematol. (1989) 42: 487-91.
(27)      Lister-James J, Knight LC, Maurer AH, Bush LR, Moyer BR and Dean RT. Thrombus imaging with a technetium-99m-labeled, activated platelet receptor-binding peptide. J. Nucl. Med. (1996) 37: 775-80.
(28)      Becker W, Börner W and Borst U. 99Tcm hexamethylpropyleneamineoxime (HMPAO) as a platelet label: evaluation of labelling parameters and first in-vivo results. Nucl. Med. Commun. (1988).
(29)      Bozlar U, Ors F, Deniz O, Uzun M, Gumus S, Ugurel MS, Yazar F and Tayfun C. Pulmonary artery diameters measured by multidetector-row computed tomography in healthy adults. Acta Radiol. (2007) 48: 1086-91.
(30)      Coche E, Pawlak S, Dechambre S and Maldague B. Peripheral pulmonary arteries: identification at multi-slice spiral CT with 3D reconstruction. Eur. Radiol. (2003) 13: 815-22.
(31)      Ray BS and Dunbar HS. Thrombosis of the dural venous sinuses as a cause of “pseudotumor cerebri”. Ann. surg. (1951) 134: 376-86.
(32)      Bernacki J, Dobrowolska A, Nierwinska K and Malecki A. Physiology and pharmacological role of the blood-brain barrier. Pharmacol. Rep. (2008) 60: 600-22.
(33)      Davidson BL, Elliott CG and Lensing AW. Low accuracy of color Doppler ultrasound in the detection of proximal leg vein thrombosis in asymptomatic high-risk patients. Ann. Intern. Med. (1992) 117: 735-8.
(34)      Loud PA, Katz DS, Bruce DA, Klippenstein DL and Grossman ZD. Deep Venous Thrombosis with suspected pulmonary embolism: Detection with combined CT venography and pulmonary angiography 1. Radiology (2001) 219: 498-502.
(35)      Meaney JF, Weg JG, Chenevert TL, Stafford-Johnson D, Hamilton BH and Prince MR. Diagnosis of pulmonary embolism with magnetic resonance angiography. N. Engl. J. Med. (1997) 336: 1422-7.
(36)      Gandhi SJ, Babu S, Subramanyam P and Sundaram PS. Tc-99m macro aggregated albumin scintigraphy-indications other than pulmonary embolism: A pictorial essay. Indian. J. Nucl. Med. (2013) 28: 152-62.
(37)      Rowe S, Hawkins B, Hamilton L, Seaton BC, Buzzeo M, Henry J, Ferrell A and Wiseman B. Contrast-induced nephropathy in stroke patients undergoing ct angiography: cinister study. Crit. Care Med. (2016) 44: 257.
(38)      Ferro JM and Canhão P. Cerebral venous sinus thrombosis: update on diagnosis and management. Curr. Cardiol. Rep. (2014) 16: 523.
(39)      Leach JL, Fortuna RB, Jones BV and Gaskill-Shipley MF. Imaging of cerebral venous thrombosis: current techniques, spectrum of findings, and diagnostic pitfalls. Radiographics (2006) 26: 19-41.
(40)      Botnar RM, Perez AS, Witte S, Wiethoff AJ, Laredo J, Hamilton J, Quist W, Parsons EC Jr, Vaidya A, Kolodziej A, Barrett JA, Graham PB, Weisskoff RM, Manning WJ and Johnstone MT. In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation (2004) 109: 2023-9.
(41)      Houshmand S, Salavati A, Hess S, Ravina M and Alavi A. The role of molecular imaging in diagnosis of deep vein thrombosis. Am. J. Nucl. Med. Mol. Imaging (2013) 4: 406-25.
(42)      Davis 2nd H, Siegel BA, Sherman LA, Heaton WA and Welch MJ. Scintigraphy with 111In-labeled autologous platelets in venous thromboembolism. Radiology (1980) 136: 203-7.
(43)      Glover C, McIntire L, Brown C and Natelson E. Dynamic coagulation studies: influence of normal and abnormal platelets on clot structure formation. Thromb. Res. (1975) 7: 185-98.