The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo 123I-CLINDE SPECT imaging: A test-retest study

Ling Feng; Per Jensen; Gerda Thomsen; Agnete Dyssegaard; Claus Svarer; Lars V. Knudsen; Kirsten Møller; Carsten Thomsen; Jens D. Mikkelsen; Denis Guilloteau; Gitte M. Knudsen; Lars H. Pinborg

doi:10.2967/jnumed.116.183202

The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo ¹²³I-CLINDE SPECT imaging: A test-retest study

Ling Feng^*, Per Jensen, Gerda Thomsen, Agnete Dyssegaard, Claus Svarer, Lars V. Knudsen, Kirsten Møller, Carsten Thomsen, Jens D. Mikkelsen, Denis Guilloteau, Gitte M. Knudsen, Lars H. Pinborg

^*Corresponding author for this work

Department of Clinical Medicine

4 Citations (Scopus)

Abstract

¹²³I-CLINDE is a radiotracer developed for SPECT and targets the 18-kDa translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of central nervous system diseases. The aim of this study was to examine the test-retest variability of ¹²³I-CLINDE binding in healthy subjects. Methods: SPECT scans were acquired over 90 min in 16 healthy controls (9 women, 8 mixed-affinity binders [MABs] and 8 high-affinity binders [HABs] twice with an interval of 35 6 15 d). Arterial input functions were based on individual blood measurements in 8 subjects and a population-based approach in combination with individual whole-blood time-activity curves in the other 8 subjects. Seven brain volumes of interest were extracted and quantified by SUVs and by 2-tissue-compartment modeling for calculation of distribution volumes (VT). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. Results: The absolute PD of brain SUV and the VT had similar values. The ICC values were higher for VTs than for brain SUVs, which were both moderate to high; however, lower ICC values were observed when calculated separately for HABs and MABs. Test-retest reproducibility was higher in subjects with immediate centrifugation of blood samples. The population-based method efficiently recovered data with delayed centrifugation. The VT of a 49-y-old male HAB was 7.5 6 1.4 mL/cm3 compared with 4.6 6 1.4 mL/cm3 of a sex-and age-matched MAB. The SUVs of a 49-y-old male HAB and MAB were 1.03 6 0.14 and 0.88 6 0.15 g/mL, respectively. Conclusion: The test-retest reproducibility of ¹²³I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Because of the binding of ¹²³I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of VT from2-tissue-compartmentmodeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.

Original language	English
Journal	Journal of Nuclear Medicine
Volume	58
Issue number	6
Pages (from-to)	989-995
Number of pages	7
ISSN	0161-5505
DOIs	https://doi.org/10.2967/jnumed.116.183202
Publication status	Published - 2017

Keywords

Polymorphism
Secondgeneration TSPO tracer
TSPO imaging
Variability

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Cite this

Feng, L., Jensen, P., Thomsen, G., Dyssegaard, A., Svarer, C., Knudsen, L. V., Møller, K., Thomsen, C., Mikkelsen, J. D., Guilloteau, D., Knudsen, G. M., & Pinborg, L. H. (2017). The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo ¹²³I-CLINDE SPECT imaging: A test-retest study. Journal of Nuclear Medicine, 58(6), 989-995. https://doi.org/10.2967/jnumed.116.183202

Feng, L, Jensen, P, Thomsen, G, Dyssegaard, A, Svarer, C, Knudsen, LV, Møller, K, Thomsen, C, Mikkelsen, JD, Guilloteau, D, Knudsen, GM & Pinborg, LH 2017, 'The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo ¹²³I-CLINDE SPECT imaging: A test-retest study', Journal of Nuclear Medicine, vol. 58, no. 6, pp. 989-995. https://doi.org/10.2967/jnumed.116.183202

@article{6cab017ad1f849599692b473bda6357c,

title = "The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo 123I-CLINDE SPECT imaging: A test-retest study",

abstract = "123I-CLINDE is a radiotracer developed for SPECT and targets the 18-kDa translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of central nervous system diseases. The aim of this study was to examine the test-retest variability of 123I-CLINDE binding in healthy subjects. Methods: SPECT scans were acquired over 90 min in 16 healthy controls (9 women, 8 mixed-affinity binders [MABs] and 8 high-affinity binders [HABs] twice with an interval of 35 6 15 d). Arterial input functions were based on individual blood measurements in 8 subjects and a population-based approach in combination with individual whole-blood time-activity curves in the other 8 subjects. Seven brain volumes of interest were extracted and quantified by SUVs and by 2-tissue-compartment modeling for calculation of distribution volumes (VT). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. Results: The absolute PD of brain SUV and the VT had similar values. The ICC values were higher for VTs than for brain SUVs, which were both moderate to high; however, lower ICC values were observed when calculated separately for HABs and MABs. Test-retest reproducibility was higher in subjects with immediate centrifugation of blood samples. The population-based method efficiently recovered data with delayed centrifugation. The VT of a 49-y-old male HAB was 7.5 6 1.4 mL/cm3 compared with 4.6 6 1.4 mL/cm3 of a sex-and age-matched MAB. The SUVs of a 49-y-old male HAB and MAB were 1.03 6 0.14 and 0.88 6 0.15 g/mL, respectively. Conclusion: The test-retest reproducibility of 123I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Because of the binding of 123I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of VT from2-tissue-compartmentmodeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.",

keywords = "Polymorphism, Secondgeneration TSPO tracer, TSPO imaging, Variability",

author = "Ling Feng and Per Jensen and Gerda Thomsen and Agnete Dyssegaard and Claus Svarer and Knudsen, {Lars V.} and Kirsten M{\o}ller and Carsten Thomsen and Mikkelsen, {Jens D.} and Denis Guilloteau and Knudsen, {Gitte M.} and Pinborg, {Lars H.}",

year = "2017",

doi = "10.2967/jnumed.116.183202",

language = "English",

volume = "58",

pages = "989--995",

journal = "The Journal of Nuclear Medicine",

issn = "0161-5505",

publisher = "Society of Nuclear Medicine",

number = "6",

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TY - JOUR

T1 - The variability of translocator protein signal in brain and blood of genotyped healthy humans using in vivo 123I-CLINDE SPECT imaging

T2 - A test-retest study

AU - Feng, Ling

AU - Jensen, Per

AU - Thomsen, Gerda

AU - Dyssegaard, Agnete

AU - Svarer, Claus

AU - Knudsen, Lars V.

AU - Møller, Kirsten

AU - Thomsen, Carsten

AU - Mikkelsen, Jens D.

AU - Guilloteau, Denis

AU - Knudsen, Gitte M.

AU - Pinborg, Lars H.

PY - 2017

Y1 - 2017

N2 - 123I-CLINDE is a radiotracer developed for SPECT and targets the 18-kDa translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of central nervous system diseases. The aim of this study was to examine the test-retest variability of 123I-CLINDE binding in healthy subjects. Methods: SPECT scans were acquired over 90 min in 16 healthy controls (9 women, 8 mixed-affinity binders [MABs] and 8 high-affinity binders [HABs] twice with an interval of 35 6 15 d). Arterial input functions were based on individual blood measurements in 8 subjects and a population-based approach in combination with individual whole-blood time-activity curves in the other 8 subjects. Seven brain volumes of interest were extracted and quantified by SUVs and by 2-tissue-compartment modeling for calculation of distribution volumes (VT). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. Results: The absolute PD of brain SUV and the VT had similar values. The ICC values were higher for VTs than for brain SUVs, which were both moderate to high; however, lower ICC values were observed when calculated separately for HABs and MABs. Test-retest reproducibility was higher in subjects with immediate centrifugation of blood samples. The population-based method efficiently recovered data with delayed centrifugation. The VT of a 49-y-old male HAB was 7.5 6 1.4 mL/cm3 compared with 4.6 6 1.4 mL/cm3 of a sex-and age-matched MAB. The SUVs of a 49-y-old male HAB and MAB were 1.03 6 0.14 and 0.88 6 0.15 g/mL, respectively. Conclusion: The test-retest reproducibility of 123I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Because of the binding of 123I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of VT from2-tissue-compartmentmodeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.

AB - 123I-CLINDE is a radiotracer developed for SPECT and targets the 18-kDa translocator protein (TSPO). TSPO is upregulated in glial cells and used as a measure of neuroinflammation in a variety of central nervous system diseases. The aim of this study was to examine the test-retest variability of 123I-CLINDE binding in healthy subjects. Methods: SPECT scans were acquired over 90 min in 16 healthy controls (9 women, 8 mixed-affinity binders [MABs] and 8 high-affinity binders [HABs] twice with an interval of 35 6 15 d). Arterial input functions were based on individual blood measurements in 8 subjects and a population-based approach in combination with individual whole-blood time-activity curves in the other 8 subjects. Seven brain volumes of interest were extracted and quantified by SUVs and by 2-tissue-compartment modeling for calculation of distribution volumes (VT). Test-retest variability was measured by percentage difference (PD), the absolute PD, intraclass correlation coefficient (ICC), and coefficient of variation. Results: The absolute PD of brain SUV and the VT had similar values. The ICC values were higher for VTs than for brain SUVs, which were both moderate to high; however, lower ICC values were observed when calculated separately for HABs and MABs. Test-retest reproducibility was higher in subjects with immediate centrifugation of blood samples. The population-based method efficiently recovered data with delayed centrifugation. The VT of a 49-y-old male HAB was 7.5 6 1.4 mL/cm3 compared with 4.6 6 1.4 mL/cm3 of a sex-and age-matched MAB. The SUVs of a 49-y-old male HAB and MAB were 1.03 6 0.14 and 0.88 6 0.15 g/mL, respectively. Conclusion: The test-retest reproducibility of 123I-CLINDE is comparable or better than that reported for commonly used PET TSPO tracers. Because of the binding of 123I-CLINDE to blood cells and peripheral tissues, SUV is not a sufficient surrogate of VT from2-tissue-compartmentmodeling. The population-adjusted method has the potential to reduce the complexity of blood analyses of TSPO tracers.

KW - Polymorphism

KW - Secondgeneration TSPO tracer

KW - TSPO imaging

KW - Variability

U2 - 10.2967/jnumed.116.183202

DO - 10.2967/jnumed.116.183202

M3 - Journal article

C2 - 28572290

AN - SCOPUS:85020221596

SN - 0161-5505

VL - 58

SP - 989

EP - 995

JO - The Journal of Nuclear Medicine

JF - The Journal of Nuclear Medicine

IS - 6

ER -