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Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment

PURPOSE: Osteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of (99m)Tc-maraciclatide, a radiopharmaceutical targeting α(v)β(3) integrin, occurs in prostate cancer (PCa) bone me...

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Autores principales: Cook, Gary J. R., Azad, Gurdip K., Taylor, Benjamin P., Lee, Eugene, Morrison, Matthew S., Hughes, Simon, Morris, Stephen, Rudman, Sarah, Chowdhury, Simon, Goh, Vicky
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915496/
https://www.ncbi.nlm.nih.gov/pubmed/29396636
http://dx.doi.org/10.1007/s00259-017-3926-7
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author Cook, Gary J. R.
Azad, Gurdip K.
Taylor, Benjamin P.
Lee, Eugene
Morrison, Matthew S.
Hughes, Simon
Morris, Stephen
Rudman, Sarah
Chowdhury, Simon
Goh, Vicky
author_facet Cook, Gary J. R.
Azad, Gurdip K.
Taylor, Benjamin P.
Lee, Eugene
Morrison, Matthew S.
Hughes, Simon
Morris, Stephen
Rudman, Sarah
Chowdhury, Simon
Goh, Vicky
author_sort Cook, Gary J. R.
collection PubMed
description PURPOSE: Osteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of (99m)Tc-maraciclatide, a radiopharmaceutical targeting α(v)β(3) integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy. METHODS: The study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with (99m)Tc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone. Tumour to normal bone (T:N) ratios, tumour to muscle (T:M) ratios and CT Hounsfield units (HU) were measured in up to five target metastases in each subject. An oncologist blinded to study scans assessed clinical responses up to 24 weeks using conventional criteria. RESULTS: Before treatment, metastases showed specific (99m)Tc-maraciclatide accumulation (mean planar T:N and T:M ratios 1.43 and 3.06; SPECT T:N and T:M ratios 3.1 and 5.19, respectively). Baseline sclerotic lesions (389–740 HU) showed lower T:M ratios (4.22 vs. 7.04, p = 0.02) than less sclerotic/lytic lesions (46–381 HU). Patients with progressive disease (PD; n = 5) showed increased planar T:N and T:M ratios (0.29 and 12.1%, respectively) and SPECT T:N and T:M ratios (11.9 and 20.2%, respectively). Patients without progression showed decreased planar T:N and T:M ratios (0.27 and −8.0%, p = 1.0 and 0.044, respectively) and SPECT T:N and T:M ratios (−21.9, and −27.2%, p = 0.3 and 0.036, respectively). The percentage change in CT HU was inversely correlated with the percentage change in SPECT T:M ratios (r = −0.59, p = 0.006). CONCLUSIONS: (99m)Tc-maraciclatide accumulates in PCa bone metastases in keeping with increased α(v)β(3) integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12 weeks of treatment differed between patients with and without PD and (99m)Tc-maraciclatide imaging may be a potential method for assessing early response.
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spelling pubmed-59154962018-04-30 Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment Cook, Gary J. R. Azad, Gurdip K. Taylor, Benjamin P. Lee, Eugene Morrison, Matthew S. Hughes, Simon Morris, Stephen Rudman, Sarah Chowdhury, Simon Goh, Vicky Eur J Nucl Med Mol Imaging Original Article PURPOSE: Osteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of (99m)Tc-maraciclatide, a radiopharmaceutical targeting α(v)β(3) integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy. METHODS: The study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with (99m)Tc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone. Tumour to normal bone (T:N) ratios, tumour to muscle (T:M) ratios and CT Hounsfield units (HU) were measured in up to five target metastases in each subject. An oncologist blinded to study scans assessed clinical responses up to 24 weeks using conventional criteria. RESULTS: Before treatment, metastases showed specific (99m)Tc-maraciclatide accumulation (mean planar T:N and T:M ratios 1.43 and 3.06; SPECT T:N and T:M ratios 3.1 and 5.19, respectively). Baseline sclerotic lesions (389–740 HU) showed lower T:M ratios (4.22 vs. 7.04, p = 0.02) than less sclerotic/lytic lesions (46–381 HU). Patients with progressive disease (PD; n = 5) showed increased planar T:N and T:M ratios (0.29 and 12.1%, respectively) and SPECT T:N and T:M ratios (11.9 and 20.2%, respectively). Patients without progression showed decreased planar T:N and T:M ratios (0.27 and −8.0%, p = 1.0 and 0.044, respectively) and SPECT T:N and T:M ratios (−21.9, and −27.2%, p = 0.3 and 0.036, respectively). The percentage change in CT HU was inversely correlated with the percentage change in SPECT T:M ratios (r = −0.59, p = 0.006). CONCLUSIONS: (99m)Tc-maraciclatide accumulates in PCa bone metastases in keeping with increased α(v)β(3) integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12 weeks of treatment differed between patients with and without PD and (99m)Tc-maraciclatide imaging may be a potential method for assessing early response. Springer Berlin Heidelberg 2018-02-02 2018 /pmc/articles/PMC5915496/ /pubmed/29396636 http://dx.doi.org/10.1007/s00259-017-3926-7 Text en © The Author(s) 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Cook, Gary J. R.
Azad, Gurdip K.
Taylor, Benjamin P.
Lee, Eugene
Morrison, Matthew S.
Hughes, Simon
Morris, Stephen
Rudman, Sarah
Chowdhury, Simon
Goh, Vicky
Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
title Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
title_full Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
title_fullStr Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
title_full_unstemmed Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
title_short Imaging α(v)β(3) integrin expression in skeletal metastases with (99m)Tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
title_sort imaging α(v)β(3) integrin expression in skeletal metastases with (99m)tc-maraciclatide single-photon emission computed tomography: detection and therapy response assessment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915496/
https://www.ncbi.nlm.nih.gov/pubmed/29396636
http://dx.doi.org/10.1007/s00259-017-3926-7
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