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Nuklearmedizin 1999; 38(03): 80-84
DOI: 10.1055/s-0038-1632196
Originalarbeiten — Original Articles
Schattauer GmbH

Improvement of Brain SPECT by Stabilization of Tc-99m-HMPAO with Methylene Blue or Cobalt Chloride

Comparison with Tc-99m-ECDVerbesserung der Hirn-SPECT durch Stabilisation von Tc-99m-HMPAO mit Methylenblau oder KobaltchloridVergleich mit Tc-99m-ECD
H. Barthel
1   Department of Nuclear Medicine, University of Leipzig and
,
I. Kämpfer
1   Department of Nuclear Medicine, University of Leipzig and
,
A. Seese
1   Department of Nuclear Medicine, University of Leipzig and
,
C. Dannenberg
1   Department of Nuclear Medicine, University of Leipzig and
,
R. Kluge
1   Department of Nuclear Medicine, University of Leipzig and
,
W. Burchert
1   Department of Nuclear Medicine, University of Leipzig and
,
W. H. Knapp
2   Medical School Hannover, Germany
› Author Affiliations
Further Information

Publication History

Received: 23 March 1998

in in revised for: 30 November 1998

Publication Date:
03 February 2018 (online)

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Summary

Aim: This present study was carried out to investigate whether stabilization of Tc-99m-HMPAO with methylene blue (MB) or cobalt chloride (CC) causes a sensible improvement in image quality and how cerebral to noncerebral activity ratios compare with those of Tc-99m-ECD. Methods: 30 minutes after preparation 400-600 MBq unstabilized Tc-99m-HMPAO (N = 35 patients), Tc-99m-HMPAO added with MB (N = 24 patients), added with CC (N = 30 patients) or Tc-99m-ECD (N = 28 patients) were injected. Radiochemical stability was measured in vitro with three chromatographical methods. Image quality was assessed quantitatively using two ratios, one of them determined by count densities of brain/scalp (QS), the other one by count densities of brain/ nose (QN). In addition, image quality (0 = bad, 3 = excellent) and background activity (0 = high, 3 = no) were visually assessed by three independent observers. Results: In contrast to unstabilized Tc-99m-HMPAO the integrity of the complexes of MB-Tc-99m-HMPAO, CC-Tc-99m-HMPAO and Tc-99m-ECD decreased only by a few percent during a period of 2 hours after reconstitution (66.8 ± 9.9 vs. 93.0 ± 2.5, 91.8 ± 1.9 and 96.9 ± 1.4%, p <0.001). Qs and Qn (m.v. ± SD) differed significantly between studies using unstabilized Tc-99m-HMPAO (3.0 ± 0.4 and 2.1 ± 0.3), MB-Tc-99m-HMPAO (3.4 ± 0.4 and 2.3 ± 0.3), CC-Tc-99m-H M PAO (3.6 ± 0.6 and 2.6 ± 0.4) and those using Tc-99m-ECD (4.3 ± 0.7 and 4.8 ± 1.4; p <0.05 and <0.001). Stabilization with CC or MB resulted in significant higher scoring of image quality and lower scoring of background activity in comparison to that of unstabilized Tc-99m-HMPAO, without reaching the scores obtained with Tc-99m-ECD. Conclusions: It is concluded that stabilization of Tc-99m-HMPAO with MB or CC definitely improves image quality in rCBF-SPECT, without reaching that of Tc-99m-ECD. Improvement of image quality results from the reduction of the amount of decomposition products that contribute to considerable extracerebral activity.

Zusammenfassung

Ziel: Mit dieser vorliegenden Studie sollte geprüft werden, ob die Stabilisierung von Tc-99m-HMPAO mit Methylenblau (MB) oder Kobaltchlorid (KC) zu einer erkennbaren Verbesserung des Bildkontrasts führt und wie das Aktivitätsverhältnis zwischen zerebralen und nichtzerebralen Strukturen im Vergleich zu Tc-99m-ECD ist. Methoden: Bei 35 Patienten wurde unstabilisiertes Tc-99m-HMPAO, bei 24 Patienten MB-Tc-99m-HMPAO, bei 30 Patienten KC-Tc-99m-HMPAO und bei 28 Patienten Tc-99m-ECD jeweils 30 min nach Präparation i.v. appliziert (jeweils 400-600 MBq). Die radiochemische Stabilität wurde in vitro mit drei chromatographischen Verfahren gemessen. Die Beurteilung der Bildqualität erfolgte (A) quantitativ (Quotient aus Impulsdichte Gehirn/ Kopfschwarte (QK) und Gehirn/Nasenraum (QN)) und (B) visuell (drei unabhängige Experten, Grad 0-3 für Bildqualität der Szintigramme und für extrakranielle Aktivität). Ergebnisse: Während die Stabilität des unstabilisierten Tc-99m-HMPAO im Untersuchungszeitraum deutlich sank, war 2 Stunden nach Rekonstitution bei MB-Tc-99m-HMPAO, KC-Tc-99rm-HMPAO und Tc-99m-ECD nur ein geringer Abfall des Anteils an primärem Komplex zu verzeichnen (66,8 ± 9,9 vs. 93,0 ± 2,5, 91,8 ± 1,9 und 96,9 ± 1,4%, p <0,001). Signifikante Unterschiede bezüglich Q k und Q n (MW ± SD) waren zwischen den Studien mit unstabilisiertem Tc-99m-HMPAO (3,0 ± 0,4 und 2,1 ± 0,3), MB-Tc-99m-HMPAO (3,4 ± 0,4 und 2,3 ± 0,3), KC-Tc-99m-HMPAO (3,6 ± 0,6 und 2,6 ± 0,4) und mit Tc-99m-ECD (4,3 ± 0,7 und 4,8 ± 1,4; p <0,05 und <0,001) zu verzeichnen. Die Stabilisierung von Tc-99m-HMPAO mit KC oder MB führte zu einer signifikant höheren Graduierung der Bildqualität sowie zu einer signifikant niedrigeren Graduierung der extrakraniellen Aktivität im Vergleich zu unstabilisiertem Tc-99m-HMPAO, ohne daß damit die gleichen Werte erreicht wurden wie unter Verwendung von Tc-99m-ECD. Schlußfolgerung: Die Stabilisierung des Tc-99m-HMPAO-Komplexes mit Methylenblau oder Kobaltchlorid führt zu einer signifikanten Verbesserung des Aktivitätskontrasts zwischen Gehirn und extrazerebralen Strukturen, ohne daß die gleiche Bildqualität wie bei Verwendung von Tc-99m-ECD erreicht wird. Die Verbesserung der Bildqualität resultiert aus der Verminderung der Menge von Dekompositionsprodukten, welche zur extrakraniellen Aktivität beitragen.

Key words

Tc-99m-HMPAO - methylene blue - cobalt chloride - Tc-99m-ECD - in vitro stabilit

Schlüsselwörter

Tc-99m-HMPAO - Methylenblau - Kobaltchlorid - Tc-99m-ECD - In-vitro-Stabilität
 

  • REFERENCES

  • 1 Amersham Healthcare. Functional brain imaging with Cetetec and SPECT - a user’s guide. 1994
    PubMedGoogle Scholar
  • 2 Anderson AR. Tc-99m-Hexamethylenepropyleneamine oxime (Tc-99m-HMPAO): basic kinetic studies of a tracer of cerebral blood flow. Cerebrovasc Brain Metab Rev 1989; 1: 288-318.
    PubMedGoogle Scholar
  • 3 Ballinger JR, Gulenchyn KY. Alternative formulations of techntium-99m. HMPAO Int J Radiat Appl Instrum (A) 1991; 42: 315-6.
    Google Scholar
  • 4 Billinghurst MW, Abrams DN, Lawson MS. Stabilization of [99m]HMPAO - 1. Ethanolic preparation. Int J Radiat Appl Instrum (A) 1991; 42: 607-12.
    CrossrefPubMedGoogle Scholar
  • 5 Ceretec package insert. Amersham International pic. 1989
    PubMedGoogle Scholar
  • 6 Costa DC, Ell PJ, Cullum ID. et al. The in vivo distribution of 99mTc-HMPAO in normal man. Nucl Med Commun 1986; 7: 647-58.
    CrossrefPubMedGoogle Scholar
  • 7 Ding HY, Yeh SJ, Yang CC. et al. Study of decomposition kinetics od Tc-99m-d,l- HMPAO complex in aqueous solution. Appl Radiat Isot 1997; 48 (03) 311-7.
    CrossrefGoogle Scholar
  • 8 Ell PJ, Cullum I, Costa DC. et al. A new regional cerebral blood flow mapping with Tc-99m-labelled compound. Lancet 1985; II: 50-1.
    PubMedGoogle Scholar
  • 9 Gartshore G, Bannan P. et al. Evaluation of technetium-99m exametazime stabilised with cobalt chloride as a blood flow tracer in focal cerebral ischaemia. Eur J Nucl Med 1994; 21: 913-23.
    PubMedGoogle Scholar
  • 10 Hung JC, Corlija M, Volkert WA. et al. Kinetic analysis of technetium-99m d,l-HMPAO decomposition in aqueous media. J Nucl Med 1988; 29: 1568-76.
    PubMedGoogle Scholar
  • 11 Hung JC, Volkert WA, Holmes RA. Stabilization of techntium-99m-D,L-hexamethylpropyleneamine oxime (99mTc-D,L-HMPAO) using gentisic acid. Int J Radiat Appl Instrum (B) 1989; 16: 675-80.
    CrossrefGoogle Scholar
  • 12 Iwamoto J, Yoshinaga M, Yang SP. et al. Methylene blue inhibits hypoxic cerebral vasodilation in awake sheep. J Appl Physiol 1992; 73 (06) 2226-32.
    CrossrefPubMedGoogle Scholar
  • 13 Lang J, Barbaries E, Lazar J. et al. Effects of labeling conditions and formulations of kit on in vitro stability of 99mTc-d,l- HM-PAO. Eur J Nucl Med 1989; 15: 424.
    Google Scholar
  • 14 Lang J, Barbaries E, Lazar J. et al. A novel d,l-HM-PAO kit formulation providing high in vitro lipophilic complex stability. Eur J Nucl Med 1990; 16: 541.
    Google Scholar
  • 15 Léveillé J., Demonceau G, Walovitch RC. Intrasubject comparison between Technetium-99m-ECD and Technetium-99m-HMPAO in healthy human subjects. J Nucl Med 1992; 33: 480-4.
    PubMedGoogle Scholar
  • 16 Lucignani G, Rossetti C, Ferrario P. et al. In vivo metabolism and kinetics of (99mTc) HM-PAO. Eur J Nucl Med 1990; 16: 249-55.
    CrossrefPubMedGoogle Scholar
  • 17 Man’gera KO, Vanbilloen HP. et al. Stabilisation of high-activity Tc-99m-d,l-HMPAO preparations with cobalt chloride and their biological behaviour. Eur J Nucl Med 1995; 22: 1163-72.
    CrossrefPubMedGoogle Scholar
  • 18 Matsuda H, Li YM. et al. Comparative Spect study of stroke using Tc-99m-ECD, 1-123-IMP, and Tc-99m-HMPAO. Clin Nucl Med 1993; 18 (09) 754-8.
    CrossrefPubMedGoogle Scholar
  • 19 Moretti JL, Defer G, Cinotti L. et al. Comparative tomoscintigraphic study of strokes using ECD Tc-99m, HMPAO Tc-99m and IMP 1-123, preliminary results (abstract). Eur J Nucl Med 1988; 14 (5/6) 311.
    Google Scholar
  • 20 Neirinckx R, Canning L, Piper I. et al. Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion. J Nucl Med 1987; 28: 191-202.
    PubMedGoogle Scholar
  • 21 Neurolite pack leaflet. DuPont Pharma GmbH; 1993
    Google Scholar
  • 22 Payne JK, Trivedi MH, Devous MD. Comparison of Technetium-99m-HMPAO and Xenon-133 measurements of regional cerebral blood flow by SPECT. J Nucl Med 1996; 37: 1735-40.
    PubMedGoogle Scholar
  • 23 Pupi A, Castagnoli A, De Cristofaro MT. et al. Quantitative comparison between Tc-99m-HMPAO and Tc-99m-ECD: measurement of arterial input and brain retention. Eur J Nucl Med 1994; 21: 124-30.
    PubMedGoogle Scholar
  • 24 Sampson CB, Solanki C. Stabilisation of Tc-99m examtazime using ethanol and storage at a low temperature. Eur J Nucl Med 1991; 18: 532.
    Google Scholar
  • 25 Sharp PF, Schmith FW, Gummell HG. et al. Technetuim-99m HMPAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies. J Nucl Med 1986; 27: 171-7.
    PubMedGoogle Scholar
  • 26 Solanki C, Li DJ, Wong A. et al. Stabilization and multidose use of examtazime for cerebral perfusion studies. Nucl Med Commun 1994; 15: 718-22.
    CrossrefPubMedGoogle Scholar
  • 27 Weisner PS, Bower GR, Dollimore LA. et al. A method for stabilizing technetium-99m exametazime prepared from a commercial kit. Eur J Nucl Med 1993; 20: 661-6.
    PubMedGoogle Scholar