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European Journal of Nuclear Medicine and Molecular Imaging

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01-03-2004 | Original Article

Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent

Authors: Kazuko Horiuchi-Suzuki, Aya Konno, Mayumi Ueda, Yoko Fukuda, Saori Nishio, Kazuyuki Hashimoto, Hideo Saji

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 3/2004

Abstract

In spite of recent advances in bone cellular and molecular biology, there is still a poor correlation between these parameters and data obtained from bone scintigraphy. Diphosphonate derivatives radiolabelled with technetium-99m (Tc-BPs) have long been recognised as bone-seeking agents with an affinity for areas of active mineralisation. However, during clinical trials with a pH-sensitive tumour agent, the pentavalent technetium complex of dimercaptosuccinic acid [Tc(V)-DMS] showed a noticeable osteotropic character only in bone pathologies (bone metastases, Paget’s diseases) and lacked accumulation in normal mature bone. To decipher the osteotropic character of Tc(V)-DMS, a study at the cellular level was considered necessary. Moreover, to learn more about the role of Tc bone agents, acid-base regulation by bone tissue or cells was studied. First, biological parameters in body fluid were measured under systemic acidosis, induced by glucose administration, in normal and Ehrlich ascites tumour (EAT)-bearing mice. Then, in vivo biodistribution studies using Tc(V)-DMS or a conventional Tc-BP agent were carried out. The effect of glucose-mediated acidification on the skeletal distribution of the Tc agents in the mice provided valuable hints regarding the differential mediation of bone cells in skeletal tissue affinity for the agents. Thereafter, in vitro studies on osteoblast and osteoclast cells were performed and the comparative affinity of Tc(V)-DMS and Tc-BP was screened under diverse acidification conditions. Moreover, studies were also carried out on acid-base parameters related to the cellular uptake mechanism. Very specific pH-sensitive Tc(V)-DMS accumulation only in the osteoclastic system was detected, and use of Tc(V)-DMS in the differential detection of osteoblastic and osteoclastic metastases is discussed.

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Title: Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent
Authors: Kazuko Horiuchi-Suzuki
Aya Konno
Mayumi Ueda
Yoko Fukuda
Saori Nishio
Kazuyuki Hashimoto
Hideo Saji
Publication date: 01-03-2004
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 3/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-003-1364-1

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Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent

Abstract

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