Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population

Gina Kavanaugh; Jason Williams; Andrew Scott Morris; Michael L. Nickels; Ronald Walker; Norman Koglin; Andrew W. Stephens; M. Kay Washington; Sunil K. Geevarghese; Qi Liu; Dan Ayers; Yu Shyr; H. Charles Manning

doi:10.1007/s11307-016-1007-0

Utility of [¹⁸F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population

Gina Kavanaugh, Jason Williams, Andrew Scott Morris, Michael L. Nickels, Ronald Walker, Norman Koglin, Andrew W. Stephens, M. Kay Washington, Sunil K. Geevarghese, Qi Liu, Dan Ayers, Yu Shyr, H. Charles Manning

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

41 Scopus citations

Abstract

Purpose: Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[¹⁸F]fluoropropyl)-L-glutamic acid ([¹⁸F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [¹⁸F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [¹¹C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [¹⁸F]FSPG PET/CT and present the first comparison to [¹¹C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. Procedures: x_C− transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [¹⁸F]FSPG PET/CT, with seven patients also imaged with [¹¹C]acetate PET/CT. Results: x_C− transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [¹⁸F]FSPG PET/CT demonstrated a detection rate of 75 %. [¹⁸F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [¹⁸F]FSPG and [¹¹C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [¹⁸F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [¹¹C]acetate PET/CT. Conclusions: [¹⁸F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [¹⁸F]FSPG PET/CT impact on diagnosis and management of HCC. [¹⁸F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.

Original language	English (US)
Pages (from-to)	924-934
Number of pages	11
Journal	Molecular Imaging and Biology
Volume	18
Issue number	6
DOIs	https://doi.org/10.1007/s11307-016-1007-0
State	Published - Dec 1 2016
Externally published	Yes

Keywords

Cancer imaging
FSPG
HCC
PET

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

Access to Document

10.1007/s11307-016-1007-0

Cite this

Kavanaugh, G., Williams, J., Morris, A. S., Nickels, M. L., Walker, R., Koglin, N., Stephens, A. W., Washington, M. K., Geevarghese, S. K., Liu, Q., Ayers, D., Shyr, Y., & Manning, H. C. (2016). Utility of [¹⁸F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population. Molecular Imaging and Biology, 18(6), 924-934. https://doi.org/10.1007/s11307-016-1007-0

Kavanaugh, G, Williams, J, Morris, AS, Nickels, ML, Walker, R, Koglin, N, Stephens, AW, Washington, MK, Geevarghese, SK, Liu, Q, Ayers, D, Shyr, Y & Manning, HC 2016, 'Utility of [¹⁸F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population', Molecular Imaging and Biology, vol. 18, no. 6, pp. 924-934. https://doi.org/10.1007/s11307-016-1007-0

@article{46f210d063cf4f14b8b879a51e893459,

title = "Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population",

abstract = "Purpose: Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. Procedures: xC− transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT. Results: xC− transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT. Conclusions: [18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.",

keywords = "Cancer imaging, FSPG, HCC, PET",

author = "Gina Kavanaugh and Jason Williams and Morris, {Andrew Scott} and Nickels, {Michael L.} and Ronald Walker and Norman Koglin and Stephens, {Andrew W.} and Washington, {M. Kay} and Geevarghese, {Sunil K.} and Qi Liu and Dan Ayers and Yu Shyr and Manning, {H. Charles}",

note = "Publisher Copyright: {\textcopyright} 2016, World Molecular Imaging Society.",

year = "2016",

month = dec,

day = "1",

doi = "10.1007/s11307-016-1007-0",

language = "English (US)",

volume = "18",

pages = "924--934",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

number = "6",

}

TY - JOUR

T1 - Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma

T2 - First Clinical Evaluation in a US Population

AU - Kavanaugh, Gina

AU - Williams, Jason

AU - Morris, Andrew Scott

AU - Nickels, Michael L.

AU - Walker, Ronald

AU - Koglin, Norman

AU - Stephens, Andrew W.

AU - Washington, M. Kay

AU - Geevarghese, Sunil K.

AU - Liu, Qi

AU - Ayers, Dan

AU - Shyr, Yu

AU - Manning, H. Charles

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Purpose: Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. Procedures: xC− transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT. Results: xC− transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT. Conclusions: [18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.

AB - Purpose: Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations. Procedures: xC− transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT. Results: xC− transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT. Conclusions: [18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.

KW - Cancer imaging

KW - FSPG

KW - HCC

KW - PET

UR - http://www.scopus.com/inward/record.url?scp=84988697462&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84988697462&partnerID=8YFLogxK

U2 - 10.1007/s11307-016-1007-0

DO - 10.1007/s11307-016-1007-0

M3 - Article

C2 - 27677886

AN - SCOPUS:84988697462

SN - 1536-1632

VL - 18

SP - 924

EP - 934

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 6

ER -