Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells.

S Auletta,A Devillers,F Galli,A Signore,N Lepareur,V Iodice

doi:10.1155/2018/5603902

Abstract

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99mTc-SSS-complex than 99mTc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p=0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p=0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p=ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p=0.001). In conclusion, 99mTc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99mTc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.

Highlights

IntroductionIn 1970s, a method for imaging of infections/in ammation, based on the ex vivo labelling of autologous leukocytes with Indium-111 (111In), was developed by akur and colleagues [1,2,3]
Erefore, new methodologies were developed to replace 111In with 99mTc for ex vivo cell labelling, and in 1986, 99mTcHMPAO entered in clinical practice for white blood cells (WBCs) radiolabelling and imaging of occult sites of infection [7]. 99mTc-HMPAO is less toxic than 111In-oxine to WBC, providing a better image quality and isotope availability
Both showed higher radiochemical purity than 99mTc-HMPAO, but only 99mTc-d,l-CBPAO provided a comparable binding to WBC

Summary

Introduction

In 1970s, a method for imaging of infections/in ammation, based on the ex vivo labelling of autologous leukocytes with Indium-111 (111In), was developed by akur and colleagues [1,2,3]. Erefore, new methodologies were developed to replace 111In with 99mTc for ex vivo cell labelling, and in 1986, 99mTcHMPAO entered in clinical practice for WBC radiolabelling and imaging of occult sites of infection [7]. In 90s, ethyl cysteinate dimer (ECD) and d,l-cyclobutylpropylene amine oxime (d,l-CBPAO) were labelled with 99mTc, and their labelling e ciency and stability were compared with 99mTc-HMPAO Both showed higher radiochemical purity than 99mTc-HMPAO, but only 99mTc-d,l-CBPAO provided a comparable binding to WBC. Erefore, in the present study, we performed the radiolabelling with 99mtechnetium of SSS-complex and tested its radiochemical purity, stability, binding specificity, and kinetics to different blood cell subsets as compared to 99mTc-HMPAO

Objectives

Methods

Results