Lars Poulsen Tolbod

The relationship between tumor aggressiveness and cholinergic PET imaging in prostate cancer tissue. A proof-of-concept study

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The relationship between tumor aggressiveness and cholinergic PET imaging in prostate cancer tissue. A proof-of-concept study. / Nielsen, Maria M; Tolbod, Lars P; Borre, Michael; Høyer, Søren; Harms, Hendrik J; Sørensen, Jens; Frøkiær, Jørgen; Borghammer, Per.

In: American Journal of Nuclear Medicine and Molecular Imaging, Vol. 9, No. 3, 2019, p. 185-192.

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@article{ede175b3eee84d1c8a816c7457129432,
title = "The relationship between tumor aggressiveness and cholinergic PET imaging in prostate cancer tissue. A proof-of-concept study",
abstract = "It was recently shown that high-risk prostate carcinoma (PCa) exhibited parasympathetic neurogenesis. The PET tracer 11C-donepezil is a marker of parasympathetic innervation. Therefore, we studied if parasympathetic nerve density in PCa measured with 11C-donepezil PET correlated with PCa aggressiveness and if metastases could be visualized. Twenty-six patients were included into three groups with varying tumor aggressiveness. Dynamic and static PET scans were performed. Maximal standardized uptake values (SUVmax) were determined in lesions within the prostate, lymph nodes, and bones. SUVmax in primary PCa were compared between groups, and comparisons between SUVmax and Gleason score and Prostate-specific antigen (PSA) were performed. Kinetic modelling was performed and time-activity curves of healthy tissue and tumor tissue fitted and compared. Tumor kinetic parameters were normalized to those of healthy tissue producing ratios of K1 and k2. Median SUVmax in primary PCa was higher in high-grade compared to low-grade PCa (P = 0.052). No correlation was seen between Gleason score and SUVmax (P = 0.28). A trend-level correlation was seen between PSA and SUVmax (P = 0.078). Median SUVmax was 7.7 (4.7-22.5) for suspected lymph node metastases and 8.2 (5.4-14.8) for suspected bone metastases. A significant difference was seen between time-activity tissue curves for low- and high-grade PCa (P = 0.012). Highly significant differences were seen in K1- and k2-ratios between low- and high-grade PCa (P = 0.0006 and P < 0.0001). We showed that 11C-donepezil accumulates in primary PCa and metastases. Simple SUVmax values of the cancer hot spots were higher in high-risk tumors compared to low-risk tumors. Further studies should elucidate the importance of cholinergic neurogenesis for prostate cancer biology.",
author = "Nielsen, {Maria M} and Tolbod, {Lars P} and Michael Borre and S{\o}ren H{\o}yer and Harms, {Hendrik J} and Jens S{\o}rensen and J{\o}rgen Fr{\o}ki{\ae}r and Per Borghammer",
year = "2019",
language = "English",
volume = "9",
pages = "185--192",
journal = "American Journal of Nuclear Medicine and Molecular Imaging",
issn = "2160-8407",
publisher = "E-Century Publishing Corporation",
number = "3",

}

RIS

TY - JOUR

T1 - The relationship between tumor aggressiveness and cholinergic PET imaging in prostate cancer tissue. A proof-of-concept study

AU - Nielsen, Maria M

AU - Tolbod, Lars P

AU - Borre, Michael

AU - Høyer, Søren

AU - Harms, Hendrik J

AU - Sørensen, Jens

AU - Frøkiær, Jørgen

AU - Borghammer, Per

PY - 2019

Y1 - 2019

N2 - It was recently shown that high-risk prostate carcinoma (PCa) exhibited parasympathetic neurogenesis. The PET tracer 11C-donepezil is a marker of parasympathetic innervation. Therefore, we studied if parasympathetic nerve density in PCa measured with 11C-donepezil PET correlated with PCa aggressiveness and if metastases could be visualized. Twenty-six patients were included into three groups with varying tumor aggressiveness. Dynamic and static PET scans were performed. Maximal standardized uptake values (SUVmax) were determined in lesions within the prostate, lymph nodes, and bones. SUVmax in primary PCa were compared between groups, and comparisons between SUVmax and Gleason score and Prostate-specific antigen (PSA) were performed. Kinetic modelling was performed and time-activity curves of healthy tissue and tumor tissue fitted and compared. Tumor kinetic parameters were normalized to those of healthy tissue producing ratios of K1 and k2. Median SUVmax in primary PCa was higher in high-grade compared to low-grade PCa (P = 0.052). No correlation was seen between Gleason score and SUVmax (P = 0.28). A trend-level correlation was seen between PSA and SUVmax (P = 0.078). Median SUVmax was 7.7 (4.7-22.5) for suspected lymph node metastases and 8.2 (5.4-14.8) for suspected bone metastases. A significant difference was seen between time-activity tissue curves for low- and high-grade PCa (P = 0.012). Highly significant differences were seen in K1- and k2-ratios between low- and high-grade PCa (P = 0.0006 and P < 0.0001). We showed that 11C-donepezil accumulates in primary PCa and metastases. Simple SUVmax values of the cancer hot spots were higher in high-risk tumors compared to low-risk tumors. Further studies should elucidate the importance of cholinergic neurogenesis for prostate cancer biology.

AB - It was recently shown that high-risk prostate carcinoma (PCa) exhibited parasympathetic neurogenesis. The PET tracer 11C-donepezil is a marker of parasympathetic innervation. Therefore, we studied if parasympathetic nerve density in PCa measured with 11C-donepezil PET correlated with PCa aggressiveness and if metastases could be visualized. Twenty-six patients were included into three groups with varying tumor aggressiveness. Dynamic and static PET scans were performed. Maximal standardized uptake values (SUVmax) were determined in lesions within the prostate, lymph nodes, and bones. SUVmax in primary PCa were compared between groups, and comparisons between SUVmax and Gleason score and Prostate-specific antigen (PSA) were performed. Kinetic modelling was performed and time-activity curves of healthy tissue and tumor tissue fitted and compared. Tumor kinetic parameters were normalized to those of healthy tissue producing ratios of K1 and k2. Median SUVmax in primary PCa was higher in high-grade compared to low-grade PCa (P = 0.052). No correlation was seen between Gleason score and SUVmax (P = 0.28). A trend-level correlation was seen between PSA and SUVmax (P = 0.078). Median SUVmax was 7.7 (4.7-22.5) for suspected lymph node metastases and 8.2 (5.4-14.8) for suspected bone metastases. A significant difference was seen between time-activity tissue curves for low- and high-grade PCa (P = 0.012). Highly significant differences were seen in K1- and k2-ratios between low- and high-grade PCa (P = 0.0006 and P < 0.0001). We showed that 11C-donepezil accumulates in primary PCa and metastases. Simple SUVmax values of the cancer hot spots were higher in high-risk tumors compared to low-risk tumors. Further studies should elucidate the importance of cholinergic neurogenesis for prostate cancer biology.

M3 - Journal article

C2 - 31328024

VL - 9

SP - 185

EP - 192

JO - American Journal of Nuclear Medicine and Molecular Imaging

JF - American Journal of Nuclear Medicine and Molecular Imaging

SN - 2160-8407

IS - 3

ER -