In Vitro Interaction between Venous Blood Clots and Radiopharmaceuticals

V. Kempi; B. R. R. Persson

doi:10.1055/s-0038-1624299

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 1985; 24(04): 173-179
DOI: 10.1055/s-0038-1624299

Originalarbeiten - Original Articles

Schattauer GmbH

In Vitro Interaction between Venous Blood Clots and Radiopharmaceuticals

In-vitro-Interaktion zwischen venösen Blutgerinnseln und Radiopharmazeutika

Authors

V. Kempi

^*From the Department of Radiophysics, Sjukhuset, Östersund
B. R. R. Persson

¹The Dept. of Radiation Physics, Lasarettet, Lund, Sweden

Abstract

Summary

Clots of 1 ml venous blood formed in glass tubes after 10 min at room temperature were incubated at 37° C with the radiopharmaceutical to be studied. Methods for quality control of the radiopharmaceuticals were compared. Gel chromatography scanning was found to give reliable information. The incorporation into the clot was studie’d at different pH values and after various time intervals. The highest incorporation was found for ¹²⁵I-fibrinogen and for ^99mTc-mac-roaggregates of albumin, followed by ^99mTc-sulphur colloid and ^99mTc-strep-tokinase at pH less than 2. The titrated initial dose of ^99mTc-streptoki-nase was studied at various pH levels. The lysing effect was less in the pH range 1-2.5, where the best labeling yield was obtained. The inactivation of streptokinase by the labeling procedure was also studied with im-munoelectrophoresis and decomposition of casein. In vitro studies of the interaction of radiopharmaceuticals with clots add information for the clinical use of radiopharmaceuticals for thrombus localization.

Zusammenfassung

Gerinnsel aus 1 ml venosem Blut wurden in Glasröhrchen nach 10 min bei Raumtemperatur gebildet und bei 37° C mit dem zu untersuchenden Radiopharmazeutikum inkubiert. Methoden der Qualitätskontrolle von Radiopharmazeutika wurden verglichen. Gelchromatographie-Scanning ergab zuverlässige Informa-tionen. Die Inkorporation in den Blut-pfropfen wurde bei unterschiedlichen pH-Werten und nach verschiedenen Zeitabständen untersucht. Die höch-ste Inkorporation fand sich bei ¹²⁵J-Fibrinogen und bei ^99mTc-Makroaggregaten von Albumin, gefolgt von ^99mTc-Schwefelkolloid und ^99mTc-Streptokinase bei einem pH <2. Die titrierte Initialdosis von ^99mTc-Strepto-kinase wurde bei verschiedenen pH-Werten untersucht. Der Lyseeffekt war geringer im pH-Bereich 1-2,5, wo die besten Markierungsausbeuten er-halten wurden. Die Inaktivierung von Streptokinase durch das Markierungs-verfahren wurde auch mit der Immun-elektrophorese und anhand des Abbaus von Kasein untersucht. In-vitro-Untersuchungen der Interaktion von Radiopharmazeutika mit Blutgerinnseln ergaben zusätzliche Informationen zur klinischen Anwendungen von Radiopharmazeutika zur Lokalisation von Thromben.

Full Text

References

REFERENCES
1 Asavavekinkul S., Forbes C. D., McDougall I. R.. Is ^99mTc-urokinase a useful agent for detection of deep venous thrombosis?. Clin. nucl. Med. 1977; 02: 235-8.
2 Atkins P., Hawkins L. A.. The diagnosis of deep-vein thrombosis of the leg using ¹²⁵I-fibrinogen. Brit. J. Surg. 1968; 55: 825-30.
3 Barfeld P. A., Rand J., Goldsmith S. J.. The use of ^99mtechnetium sulfur colloid as a marker for experimental venous thrombosis. J. nucl. Med. 1981; 22: 598-600.
4 Barfeld P. A., Harrison D. A., Wasserstein G., Buetow G., Irvin G. A. L.. Work in Progress: Detection of Deep Venous Thrombosis with ^99mTc-Sulfur Colloid. Radiology 1983; 146: 185-9.
5 Bernstein K.. A new ^l25I-fibrinogen technique for detection and depth localization of post-operative venous thrombosis. Studies in patients subjected to gynecologic surgery. 1981. Thesis. Malmö; Sweden.:
6 Darte L.. Quality control of ^99mtechnetium radiopharmaceuticals in nuclear medicine. 1981. Thesis. Dept of Radiation Physics, Lasarettet; Lund, Sweden.:
7 Darte L., Olsson C. G., Persson R. B. R.. ^99mTc-labelling of streptokinase and its use for detection of deep vein thrombosis using scintillation camera or hand detector. In: Proc 13th Int. Ann. Meeting, Soc. nucl. Med., Copenhagen, 10-13 Sept, 1975.. 1977. Schattauer Verlag; Stuttgart - New York.:
8 Duffy M. J., Duffy G. J.. Studies on the Labeling of Streptokinase with ^99mTc for Use as a Radiopharmaceutical in the Detection of Deep-Vein Thrombosis. J. nucl. Med. 1977; 18: 483-5.
9 Dugan M. A., Kozar J. J., Ganze G., Charkes N. D.. Localization of deep vein thrombosis using radioactive streptokinase. J. nucl. Med. 1973; 14: 233-4.
10 Eckelman W. C., Richards P.. Analytical pitfalls with ^99mTc-labeled compounds. J. nucl. Med. 1972; 13: 202-4.
11 Edenbrandt C-M., Dahlström J. A., Nilsson J., Ohlin P.. Comparison between ^99mTc-porcine plasmin and ^99mrelabelled erythrocytes in diagnosis of deep vein thrombosis. Clin. Phys. 1984; 04: 243-52.
12 Goodman L. R., Goodman C., Greenspan R. H., Porter C. D.. Failure to Visualize Experimentally Produced Emboli and Thrombi Using ¹³¹I Streptokinase. Invest. Radiol. 1973; 08: 377-83.
13 Gross R.. Findings with labelled streptokinase in vitro and in vivo. In: Proc., Ninth Congr. Europ. Soc. Haematol.. 1963. Lisbon; Karger, Basel: 11342-5.
14 Kempi V., van der Linden W., von Schéele C.. Diagnosis of deep-vein thrombosis with ^99mTc-streptokinase: A clinical comparison with phlebography. Brit. med. J. 1974; 04: 748-9.
15 Kempi V., van der Linden W., von Schéele C.. Uptake of ^99mTc-tripolyphosphate in thrombotic leg. Nucl. med. 1976; 15: 14-7.
16 Kempi V., von Schéele C.. Diagnosis of deep-vein thrombosis with sodium pertechnetate. J. nucl. Med. 1976; 17: 1096-9.
17 Laurell C. B.. Electroimmuno Assay. Scand. J. clin. Lab. Invest. 1972; 29 (Suppl. 124) 21-37.
18 Nilsson I. M., Olow B.. Fibrinolysis induced by streptokinase in man. Acta Chir. Scand. 1962; 123: 247-66.
19 Olsson C-G., Albrechtsson U., Darte L., Persson R. B.R.. ^99mTc-plasmin for rapid detection of deep vein thrombosis. Nucl. med. Commun. 1982; 03: 41-52.
20 Ouchi H., Warren R.. Detection of intravascular thrombi by means of ¹³¹I-labeled plasmin. Surgery 1962; 51: 42-9.
21 Persson R. B.R.. Gel-chromatography-column-scanning (“GCS”). A method for identification and quality control of ^99mtechnetium radiopharmaceuticals. In: Proc. Int. Symp. Radiopharmaceuticals, 1974, Atlanta, Ga, USA, Soc. nucl. Med.. 1975. New York: 228.
22 Persson R. B. R., Darte L.. Labeling plasmin with ^99mtechnetium for scintigraphic localization of thrombi. Int. J. Appl. Radiat. Isot. 1977; 28: 97-104.
23 Persson R. B. R., Kempi V.. Labeling and testing of ^99mTc-streptokinase for the diagnosis of deep vein thrombosis. J. nucl. Med. 1975; 16: 474-7.
24 Remmert L. F., Cohen P. P.. Partial purification and properties of a proteolytic enzyme of human serum. J. biol. Chem. 1949; 181: 431-48.
25 Rhodes B. A., Turaihi K. S., Bell W. R., Wagner H. N.. Radioactive urokinase for blood clot scanning. J. nucl. Med. 1972; 13: 646-8.
26 Ryo U. Y., Colombetti L. G., Polin S. G., Pinsky S. M.. Radionuclide Venography: Significance of Delayed Washout; Visualization of the Saphenous System. J. nucl. Med. 1976; 17: 590-5.
27 Siegel M. E., Malmud L. S., Rhodes B. A.. et al. Scanning of Thromboemboli with ¹³¹I-Streptokinase. Radiology 1972; 103: 695-6.
28 Stahlberg F., Andersson L., Edenbrandt C-M., Strand S-E.. Quantitative in vivo and in vitro comparison between radiolabelled colloids, biomolecules and blood cells in their ability to diagnose deep venous thrombosis. Nucl. med. Commun. 1984; 05: 741-62.
29 Vieras F., Barron E. L., Parker G. A., Grissom M. P.. Experimental evaluation of ^99mTc-sulphur colloid as a potential imaging agent in thromboembolic disease. J. nucl. Med. 1980; 21: 723-8.
30 Webber M. M., Bennet L. R., Cragin M., Webb Jr R.. Thrombophlebitis -demonstration by scintiscanning. Radiology 1969; 92: 620-3.