Tumor Sink Effect in 68Ga-PSMA-11 PET: Myth or Reality?

Andrei Gafita; Hui Wang; Andrew Robertson; Wesley R. Armstrong; Raphael Zaum; Manuel Weber; Farid Yagubbayli; Clemens Kratochwil; Tristan R. Grogan; Kathleen Nguyen; Fernando Navarro; Rouzbeh Esfandiari; Isabel Rauscher; Bjoern Menze; David Elashoff; Ebrahim S. Delpassand; Ken Herrmann; Johannes Czernin; Michael S. Hofman; Jeremie Calais; Wolfgang P. Fendler; Matthias Eiber

doi:10.2967/JNUMED.121.261906

Tumor Sink Effect in ⁶⁸Ga-PSMA-11 PET: Myth or Reality?

Andrei Gafita
, Hui Wang
, Andrew Robertson
, Wesley R. Armstrong
, Raphael Zaum
, Manuel Weber
, Farid Yagubbayli
, Clemens Kratochwil
, Tristan R. Grogan
, Kathleen Nguyen
, Fernando Navarro
, Rouzbeh Esfandiari
, Isabel Rauscher
, Bjoern Menze
, David Elashoff
, Ebrahim S. Delpassand
, Ken Herrmann
, Johannes Czernin
, Michael S. Hofman
, Jeremie Calais

Wolfgang P. Fendler, Matthias Eiber

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

We aimed to systematically determine the impact of tumor burden on ⁶⁸Ga-prostate-specific membrane antigen-11 (⁶⁸Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent ⁶⁸Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, #25 cm³), low (quintile 2, 25-189 cm³), moderate (quintile 3, 189-532 cm³), high (quintile 4, 532-1,355 cm³), or very high (quintile 5, $1,355 cm³) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using ⁶⁸Ga-PSMA PET images, and SUV_mean was obtained. Correlations between the SUV_mean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm³ (interquartile range [IQR], 47-1,076 cm³). The median SUV_mean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUV_mean of the salivary glands (r 5 20.44, P, 0.001), kidneys (r 5 20.34, P, 0.001), and liver (r 5 20.30, P, 0.001) and a weak negative correlation with the spleen SUV_mean (r 5 20.16, P 5 0.002). Patients with a very high PSMA-VOL (quintile 5, $1,355 cm³) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of 238.1%, 240.0%, 243.2%, and 234.9%, respectively (P, 0.001). Conclusion: Tumor sequestration affects ⁶⁸Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of ⁶⁸Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.

Original language	English
Pages (from-to)	226-232
Number of pages	7
Journal	Journal of Nuclear Medicine
Volume	63
Issue number	2
DOIs	https://doi.org/10.2967/JNUMED.121.261906
State	Published - 1 Feb 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Ga-PSMA
PET
PSMA
prostate cancer
radioligand therapy
tumor sink effect

Access to Document

10.2967/JNUMED.121.261906

Cite this

Gafita, A., Wang, H., Robertson, A., Armstrong, W. R., Zaum, R., Weber, M., Yagubbayli, F., Kratochwil, C., Grogan, T. R., Nguyen, K., Navarro, F., Esfandiari, R., Rauscher, I., Menze, B., Elashoff, D., Delpassand, E. S., Herrmann, K., Czernin, J., Hofman, M. S., ... Eiber, M. (2022). Tumor Sink Effect in ⁶⁸Ga-PSMA-11 PET: Myth or Reality? Journal of Nuclear Medicine, 63(2), 226-232. https://doi.org/10.2967/JNUMED.121.261906

@article{fe7dd005d7e54a76afc273a33956d2d8,

title = "Tumor Sink Effect in 68Ga-PSMA-11 PET: Myth or Reality?",

abstract = "We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, \#25 cm3), low (quintile 2, 25-189 cm3), moderate (quintile 3, 189-532 cm3), high (quintile 4, 532-1,355 cm3), or very high (quintile 5, \$1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47-1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r 5 20.44, P, 0.001), kidneys (r 5 20.34, P, 0.001), and liver (r 5 20.30, P, 0.001) and a weak negative correlation with the spleen SUVmean (r 5 20.16, P 5 0.002). Patients with a very high PSMA-VOL (quintile 5, \$1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of 238.1\%, 240.0\%, 243.2\%, and 234.9\%, respectively (P, 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.",

keywords = "Ga-PSMA, PET, PSMA, prostate cancer, radioligand therapy, tumor sink effect",

author = "Andrei Gafita and Hui Wang and Andrew Robertson and Armstrong, \{Wesley R.\} and Raphael Zaum and Manuel Weber and Farid Yagubbayli and Clemens Kratochwil and Grogan, \{Tristan R.\} and Kathleen Nguyen and Fernando Navarro and Rouzbeh Esfandiari and Isabel Rauscher and Bjoern Menze and David Elashoff and Delpassand, \{Ebrahim S.\} and Ken Herrmann and Johannes Czernin and Hofman, \{Michael S.\} and Jeremie Calais and Fendler, \{Wolfgang P.\} and Matthias Eiber",

note = "Publisher Copyright: COPYRIGHT {\textcopyright} 2022 by the Society of Nuclear Medicine and Molecular Imaging.",

year = "2022",

month = feb,

day = "1",

doi = "10.2967/JNUMED.121.261906",

language = "English",

volume = "63",

pages = "226--232",

journal = "Journal of Nuclear Medicine",

issn = "0161-5505",

publisher = "Society of Nuclear Medicine Inc.",

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Gafita, A, Wang, H, Robertson, A, Armstrong, WR, Zaum, R, Weber, M, Yagubbayli, F, Kratochwil, C, Grogan, TR, Nguyen, K, Navarro, F, Esfandiari, R, Rauscher, I, Menze, B, Elashoff, D, Delpassand, ES, Herrmann, K, Czernin, J, Hofman, MS, Calais, J, Fendler, WP & Eiber, M 2022, 'Tumor Sink Effect in ⁶⁸Ga-PSMA-11 PET: Myth or Reality?', Journal of Nuclear Medicine, vol. 63, no. 2, pp. 226-232. https://doi.org/10.2967/JNUMED.121.261906

TY - JOUR

T1 - Tumor Sink Effect in 68Ga-PSMA-11 PET

T2 - Myth or Reality?

AU - Gafita, Andrei

AU - Wang, Hui

AU - Robertson, Andrew

AU - Armstrong, Wesley R.

AU - Zaum, Raphael

AU - Weber, Manuel

AU - Yagubbayli, Farid

AU - Kratochwil, Clemens

AU - Grogan, Tristan R.

AU - Nguyen, Kathleen

AU - Navarro, Fernando

AU - Esfandiari, Rouzbeh

AU - Rauscher, Isabel

AU - Menze, Bjoern

AU - Elashoff, David

AU - Delpassand, Ebrahim S.

AU - Herrmann, Ken

AU - Czernin, Johannes

AU - Hofman, Michael S.

AU - Calais, Jeremie

AU - Fendler, Wolfgang P.

AU - Eiber, Matthias

PY - 2022/2/1

Y1 - 2022/2/1

N2 - We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, #25 cm3), low (quintile 2, 25-189 cm3), moderate (quintile 3, 189-532 cm3), high (quintile 4, 532-1,355 cm3), or very high (quintile 5, $1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47-1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r 5 20.44, P, 0.001), kidneys (r 5 20.34, P, 0.001), and liver (r 5 20.30, P, 0.001) and a weak negative correlation with the spleen SUVmean (r 5 20.16, P 5 0.002). Patients with a very high PSMA-VOL (quintile 5, $1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of 238.1%, 240.0%, 243.2%, and 234.9%, respectively (P, 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.

AB - We aimed to systematically determine the impact of tumor burden on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA) PET biodistribution by the use of quantitative measurements. Methods: This international multicenter, retrospective analysis included 406 men with prostate cancer who underwent 68Ga-PSMA PET/CT. Of these, 356 had positive findings and were stratified by quintiles into a very low (quintile 1, #25 cm3), low (quintile 2, 25-189 cm3), moderate (quintile 3, 189-532 cm3), high (quintile 4, 532-1,355 cm3), or very high (quintile 5, $1,355 cm3) total PSMA-positive tumor volume (PSMA-VOL). PSMA-VOL was obtained by semiautomatic segmentation of total tumor lesions using qPSMA software. Fifty prostate cancer patients with no PSMA-positive lesions (negative scan) served as a control group. Normal organs, which included salivary glands, liver, spleen, and kidneys, were semiautomatically segmented using 68Ga-PSMA PET images, and SUVmean was obtained. Correlations between the SUVmean of normal organs and PSMA-VOL as continuous and categoric variables by quintiles were evaluated. Results: The median PSMA-VOL was 302 cm3 (interquartile range [IQR], 47-1,076 cm3). The median SUVmean of salivary glands, kidneys, liver, and spleen was 10.0 (IQR, 7.7-11.8), 26.0 (IQR, 20.0-33.4), 3.7 (IQR, 3.0-4.7), and 5.3 (IQR, 4.0-7.2), respectively. PSMA-VOL showed a moderate negative correlation with the SUVmean of the salivary glands (r 5 20.44, P, 0.001), kidneys (r 5 20.34, P, 0.001), and liver (r 5 20.30, P, 0.001) and a weak negative correlation with the spleen SUVmean (r 5 20.16, P 5 0.002). Patients with a very high PSMA-VOL (quintile 5, $1,355 cm3) had a significantly lower PSMA uptake in the salivary glands, kidneys, liver, and spleen than did the control group, with an average difference of 238.1%, 240.0%, 243.2%, and 234.9%, respectively (P, 0.001). Conclusion: Tumor sequestration affects 68Ga-PSMA biodistribution in normal organs. Patients with a very high tumor load showed a significantly lower uptake of 68Ga-PSMA in normal organs, confirming a tumor sink effect. As similar effects might occur with PSMA-targeted radioligand therapy, these patients might benefit from increased therapeutic activity without exceeding the radiation dose limit for organs at risk.

KW - Ga-PSMA

KW - PET

KW - PSMA

KW - prostate cancer

KW - radioligand therapy

KW - tumor sink effect

UR - https://www.scopus.com/pages/publications/85116821899

U2 - 10.2967/JNUMED.121.261906

DO - 10.2967/JNUMED.121.261906

M3 - Article

C2 - 34049987

AN - SCOPUS:85116821899

SN - 0161-5505

VL - 63

SP - 226

EP - 232

JO - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

IS - 2

ER -