Editorial
Low-dose CT and contrast-medium CT in hybrid PET/CT systems for oncologic patients Agostino Chiaravallotia, Domenico Rubellob, Sotirios Chondrogiannisb, Francesco Giammariled, Patrick M. Collettie and Orazio Schillacia,c Nuclear Medicine Communications 2015, 36:867–870 a
Department of Biomedicine and Prevention, University Tor Vergata, Rome, Department of Nuclear Medicine & PET/CT Unit, Santa Maria della Misericordia Hospital, Rovigo, cIRCCS Neuromed, Pozzilli, Italy, dDepartment of Radiology, University of Southern California, Los Angeles, California, USA and eDepartment of Nuclear Medicine, Lyon University, Lyon, France b
The combination of a PET scanner and a computed tomographic (CT) scanner in the same machine has its origin in the early 1990s. The gaps between the banks of PET detectors offered the possibility of incorporating different imaging modalities in the same machine, and a source of radiographs has been chosen to ‘complete’ the ring of detectors [1]. The results of the first PET/CT prototype were impressive and attracted several vendors interested in the possibility of combining morphological and functional imaging in the same examination. The introduction of CT in a hybrid PET/CT machine eliminated the transmission scan (or attenuation scan) that was previously performed with a 68Ge source rotating around the patient for computing the attenuation produced by the patient itself. The attenuation scan was time-consuming, especially for oncological whole-body scans that are composed of 6–7 bed positions, with the 68Ge attenuation scan taking ∼ 3–10 min for every bed position. The attenuation correction based on the CT scan significantly reduced the duration of a PET scan. The first commercial PET/CT scanner to be announced was the Discovery LS (GE Healthcare, Milwaukee, Minnesota, USA) in early 2001, a design that incorporated a four-slice CT scanner; this was followed by novel machines that now incorporate the rapid advances achieved in the field of PET and CT [i.e. Philips TF (Philips, Amsterdam, Netherlands) incorporates novel LYSO PET detectors that are characterized by low energy and time resolution with a 128-slice CT]. Most of the published studies that have investigated the usefulness of PET/CT in oncology suggest that the CT in a PET/CT study can be used for diagnosis [with the injection of a contrast medium, PET/contrast-enhanced CT (ceCT)] or for anatomic localization of PET images [PET/low-dose CT (ldCT)]. An issue recently outlined when using oral and intravenous contrast agents during a PET/CT study is the probability of misinterpretation of PET/CT examinations while providing better anatomical details and showing contrast-enhanced lesions [2]. The main limitation in the use of oral contrast media in a PET/CT scan is the possible impact on the evaluation of 0143-3636 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Correspondence to Domenico Rubello, MD, Department of Nuclear Medicine & PET/CT Unit, Santa Maria della Misericordia Hospital, Viale Tre Martiri, 140, 45100 Rovigo, Italy Tel: + 39 0425 39 4428/4548; fax: + 39 0425 394434; e-mail: [email protected] Received 2 March 2015 Accepted 11 March 2015
the uptake of the PET tracer. In fact, for clinically used concentrations of oral contrast agents, phantom measurements showed an overestimation of a 2-deoxy-2-(18F) fluoro-D-glucose (18F-FDG) concentration of ∼ 4–20% [2]. However, the effect of oral CT contrast media seems to be negligible when the contrast agent is distributed homogeneously in the bowel [2], and several reports show that artifacts due to oral agents and intravenous contrast usually injected after a PET scan are easily recognizable [3]. As far as the intravenous contrast agent is concerned, a study reported artifacts in PET/CT scans due to the transient bolus passage of undiluted intravenous contrast agent [4]. Several PET/ceCT protocols have been proposed and consists, for example, of a biphasic or triple-phase injection of contrast media [5,6]. A study has been carried out to investigate whether ceCT attenuation correction could introduce artifacts in PET images. Maximum standardized uptake value has been calculated for different anatomical regions (liver, lung, spleen, etc.) and for the sites of recurrence of cancer. A mild increase in maximum standardized uptake value has been shown, especially in the sites of recurrence, when using ceCT for attenuation correction; nevertheless, the results of this study show that the use of intravenous contrast media does not introduce artifacts that could lead to the detection of a pathological increase of 18F-FDG uptake [7]. In our experience, conducting a three-phase ceCT scan at the end of a whole-body PET/ldCT scan leads to good results in terms of both image quality (fused PET with a ceCT) and diagnostic accuracy [8]. Moreover, the advantage of performing a ceCT at the end of a PET/ldCT is that the ceCT can be avoided in those patients with a negative PET/ldCT or in those with no disease located in parenchymatous organs (see below). The gain in image quality and diagnostic accuracy from a PET/ceCT is ‘balanced’ by a relatively higher radiation exposure due to the performance of a diagnostic CT rather than or in addition to a ldCT. Brix et al. [5] found that, per examination, the effective dose was ∼ 26 millisievert (mSv) for PET/ceCT versus 8.5 mSv for DOI: 10.1097/MNM.0000000000000314
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PET/ldCT. The higher radiation exposure from a PET/ceCT is actually the main limitation of this type of scan, especially in young patients (with most of them undergoing very closely spaced PET scans for the followup of hematological malignances). 18
F-FDG is the most widely used PET radiotracer in PET/CT examinations. As for staging, when imaging modalities were being compared (18F-FDG PET/ldCT vs. ceCT), the general trend was to consider PET as being superior to ceCT in the staging of several types of tumors characterized by high avidity of this radiotracer [9, 10]. Hodgkin’s lymphoma and non-Hodgkin’s lymphoma represent a category of diseases in which the use of contrast media in a PET/CT scan for both staging and restaging has been frequently discussed, mainly because of the young age at onset of the disease and the frequency of conducting PET/CT examinations during the clinical course of the disease [11]. Several studies have investigated the diagnostic performance of PET/ldCT as compared with PET/ceCT in staging to establish whether PET/ldCT could suffice in staging or restaging these patients. The superiority of PET in staging is mainly due to the recognition of pathological activity in normal-sized tissues (especially lymph nodes) and in bone marrow, where cortical abnormalities appear late during the development of the disease [8,12]. Other studies on the performance of PET and ceCT in other solid tumors lead to similar conclusions. For head and neck cancers, a recent meta-analysis that summarized the results of over 1400 PET/ldCT scans reported a sensitivity and specificity for PET/ldCT of 85 and 98%, respectively [13]; the superiority of PET/ldCT over morphologic imaging in detecting lymph node involvement is well-known [14]. PET adds significantly to the accuracy of staging of cancer in lymph nodes [15]. The major limitation of ceCT in the assessment of lymph node status across all common cancers is the use of lymph node size as the sole criterion for tumor involvement. Although a short-axis diameter larger than 1 cm and the disappearance of normal features such as hilum representation are considered positive for tumor, cancer cells are often present in lymph nodes smaller than 1 cm. The ability of PET to detect cancer in normal-sized lymph nodes and to more accurately categorize larger nodes has led to an increasing trend to prefer it over CT for nodal staging of many epithelial malignancies, including non-small-cell lung cancer [16], esophageal cancer [17], head and neck cancers [18], and cervical carcinoma [19]. Despite the higher sensitivity, the specificity of PET in assessing locoregional disease extension in a PET/ldCT examination is often limited by several factors such as the physiological uptake of 18F-FDG in normal tissues (muscles, vocal cords, brown fat) and its excretion by salivary glands, which may influence image interpretation and often leads to false-positive findings [20]. Moreover, the absence of contrast media in PET/ldCT severely
limits the distinction between lesions and the cleavage planes affecting the staging of several diseases. Pfannenberg et al. [21] found that 6% of patients with lung cancer could be correctly classified as having T4 tumors only after contrast application; in this study a different management in a significant percentage of patients has been chosen on the basis of the results of ceCT. In fact, the CT performed solely for attenuation correction does not allow the identification of cleavage planes between the primary tumor and contiguous structures such as vessels and the chest wall [21]. Strobel and colleagues investigated the accuracy of PET, PET/ldCT, and PET/ceCT in the identification of resectability in a pool of patients with pancreatic cancer. The exclusion criteria for surgery were the presence of metastasis, peritoneal carcinomatosis, and the infiltration of large vessels or adjacent organs. PET/ceCT has shown a gain in diagnostic accuracy (88%) as compared with PET (70%) and PET/ldCT (76%), as well as in specificity (82 vs. 44 and 56%); in particular, ceCT allowed the detection of liver metastasis and the invasion of large vessels that were not detectable in ldCT [22]. Another limitation of nonenhanced CT is represented by the distinction of the anatomical structures of the abdomen and pelvis where, without the use of contrast media, it is difficult to distinguish the bowel or vessels from adjacent structures, especially after surgery. In a PET/ldCT, the physiological increase in glucose consumption in the bowel and the 18F-FDG excretion in the urinary pathways severely limit the performance of PET in distinguishing physiological from pathological uptake. Hence, it is not surprising that, compared with PET/ldCT, PET/ceCT determined the status of pararectal lymph nodes, internal iliac lymph nodes, and obturator lymph nodes more correctly [23]. The diagnostic accuracy of ceCT versus ldCT in a hybrid PET/CT scan was retrospectively evaluated on 53 patients with colorectal cancer [23]. Lymph node assessment was correctly established by PET/ldCT and PET/ceCT in 70 and 79% of the patients, respectively, with an increase in specificity (42 vs. 68%) [23]. PET has been shown to be inferior to ceCT in the detection of lesions in the liver and the spleen, especially when the dimensions are smaller than 1 cm [8,12,20]. The limitations of diagnostic accuracy of PET in both the spleen and the liver resides in the spatial resolution of PET and, mainly, in movement artifacts due to normal breath, which severely limits the detection of lesions close to respiratory muscles such as the diaphragm [24]. The novel technical advances (i.e. respiratory gating) that have been introduced to avoid these motion artifacts [24], even if effective, are difficult to introduce into common clinical routine because they are often time-consuming. As for restaging, recent studies show that ceCT has a minor role in restaging lymphoproliferative disorders in a PET/CT examination, with the early assessment of
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therapy response being represented by a metabolic rather than a morphological change [11]. Several studies in fact show that the disappearance or persistence of a negligible 18 F-FDG uptake in a site of previous illness location is related to a higher disease-free survival regardless of the dimension of the residual pathological tissue [11]. Differently from hematological malignancies, ceCT changed the therapy approach in 9% of patients who underwent a PET/ldCT and a PET/ceCT examination, with the majority of the lesions missed by PET/ldCT being located in the liver [25]. The authors reported that, compared with PET/ldCT, PET/ceCT revealed additional information in 72% of patients, with a significant impact on therapeutic decisions in 42% [25]. The limitations described previously for the detection of lesions in the liver and the spleen at staging are worsened with the start of chemotherapy (CHT), with the tumor response to CHT being related to a reduced glucose consumption that makes the lesions less detectable in PET [26]. Tan and colleagues demonstrated that, at the level of the liver, cancer cells are detectable in 85% of lesions that show a disappearance of pathological glucose consumption after CHT. This suggests that, even if PET is a sensitive tool for the detection of early response to CHT, the absence of pathological metabolism does not mean a complete response to therapy [27]. Another study has shown significant reduction in 18F-FDG uptake in patients treated preoperatively with CHT, resulting in less efficient detection of cancerous lesions [28]; the sensitivity of PET/ldCT and ceCT in detecting colorectal metastases was significantly higher in CHT-naive patients, whereas ceCT had a higher sensitivity than PET/ldCT in detecting metastases following neoadjuvant therapy (65.3 vs. 49%) [29]. Other authors report an underestimation of 52% of lesions in patients with colorectal cancer who are subjected to a PET/ldCT instead of ceCT during treatment [30]; the sensitivity of PET/ldCT moves from 92 to 63% in those patients treated with CHT before examination [31]. Recently it was shown that an increased glucose consumption in the liver (probably due to toxic CHT effects) results in an increase in background activity [32]and then in difficult interpretation of PET images. Therapeutic treatments and procedures could lead to false-positive findings in PET. It has been reported that, especially after therapy, the inflammatory processes that occur in patients (generally due to surgery or radiotherapy) are a frequent cause of false-positive PET findings, as the activated inflammatory cells show increased 18F-FDG uptake. The conjunction of PET with ceCT could help in the identification of physiological 18F-FDG in normal tissues and, on the other side, the identification of pathological 18F-FDG uptake in tissues with no pathological abnormalities [33].
Several types of tumors are characterized by a low glucose consumption. When 18F-FDG PET is chosen for diagnostic purposes in cancers with a low glucose metabolic rate (i.e. for assessing the transformation of an indolent disease in a more aggressive disease [34]), the conjunction of PET/ldCT with ceCT is essential for correct staging of the disease due to the detection of pathological areas that do not show increased glucose consumption [9,35]. To our knowledge, few studies investigated the added value of ceCT in a PET/CT examination with radiotracers other than 18F-FDG, such as L-3,4-dihydroxy-611 (18F-FDOPA), Cor [18F]fluorophenylalanine 18 68 F-choline, or Ga-DOTA-TOC. These radiolabeled compounds are used, respectively, for the evaluation of primary brain tumors (18F-FDOPA), prostate cancer (11C- or 18F-choline), and neuroendocrine tumors (18F-FDOPA and 68Ga-DOTA-TOC). It is reasonable to suppose that, with few exceptions, the conjunction with a ceCT could be of help in the interpretation of PET data, especially for those anatomical sites characterized by physiological uptake of these radiotracers or where paraphysiological uptake of these compounds could lead to pitfalls in image interpretation [36,37]. As a last aspect, a recent paper investigated the economic impact of PET/ldCT and ceCT in the same examination as compared with the performance of the two imaging modalities at different times [38]. In this paper the authors analyzed the costs for the hospital and for the patients (n = 150), taking into account the direct (technology, physicians, medical staff, etc.), indirect, and social costs (loss of hours of work, travels, etc.). The results show an economic advantage for the protocol that includes the performance of a PET/ldCT and a ceCT in a single session; a significant reduction in the waiting period between the execution of PET/ldCT and ceCT was observed as well, with a significant reduction in the time to diagnosis and to begin the treatment [38]. In conclusion, the use of contrast-medium CT should be recommended for most patients with cancer for whom anatomical details are vital for correct staging of the disease or for surgical planning (i.e. invasion of large vessels or of the adjacent structures) or in the case of cancer location or recurrence in parenchymatous organs. A scrupulous selection of patients is indispensable and should take into account the higher radiation exposure of a diagnostic CT in a PET/CT examination.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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Low-dose CT and contrast-medium CT in hybrid PET/CT systems for oncologic patients Agostino Chiaravallotia, Domenico Rubellob, Sotirios Chondrogiannisb, Francesco Giammariled, Patrick M. Collettie and Orazio Schillacia,c Nuclear Medicine Communications 2015, 36:867–870 a
Department of Biomedicine and Prevention, University Tor Vergata, Rome, Department of Nuclear Medicine & PET/CT Unit, Santa Maria della Misericordia Hospital, Rovigo, cIRCCS Neuromed, Pozzilli, Italy, dDepartment of Radiology, University of Southern California, Los Angeles, California, USA and eDepartment of Nuclear Medicine, Lyon University, Lyon, France b
The combination of a PET scanner and a computed tomographic (CT) scanner in the same machine has its origin in the early 1990s. The gaps between the banks of PET detectors offered the possibility of incorporating different imaging modalities in the same machine, and a source of radiographs has been chosen to ‘complete’ the ring of detectors [1]. The results of the first PET/CT prototype were impressive and attracted several vendors interested in the possibility of combining morphological and functional imaging in the same examination. The introduction of CT in a hybrid PET/CT machine eliminated the transmission scan (or attenuation scan) that was previously performed with a 68Ge source rotating around the patient for computing the attenuation produced by the patient itself. The attenuation scan was time-consuming, especially for oncological whole-body scans that are composed of 6–7 bed positions, with the 68Ge attenuation scan taking ∼ 3–10 min for every bed position. The attenuation correction based on the CT scan significantly reduced the duration of a PET scan. The first commercial PET/CT scanner to be announced was the Discovery LS (GE Healthcare, Milwaukee, Minnesota, USA) in early 2001, a design that incorporated a four-slice CT scanner; this was followed by novel machines that now incorporate the rapid advances achieved in the field of PET and CT [i.e. Philips TF (Philips, Amsterdam, Netherlands) incorporates novel LYSO PET detectors that are characterized by low energy and time resolution with a 128-slice CT]. Most of the published studies that have investigated the usefulness of PET/CT in oncology suggest that the CT in a PET/CT study can be used for diagnosis [with the injection of a contrast medium, PET/contrast-enhanced CT (ceCT)] or for anatomic localization of PET images [PET/low-dose CT (ldCT)]. An issue recently outlined when using oral and intravenous contrast agents during a PET/CT study is the probability of misinterpretation of PET/CT examinations while providing better anatomical details and showing contrast-enhanced lesions [2]. The main limitation in the use of oral contrast media in a PET/CT scan is the possible impact on the evaluation of 0143-3636 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Correspondence to Domenico Rubello, MD, Department of Nuclear Medicine & PET/CT Unit, Santa Maria della Misericordia Hospital, Viale Tre Martiri, 140, 45100 Rovigo, Italy Tel: + 39 0425 39 4428/4548; fax: + 39 0425 394434; e-mail: [email protected] Received 2 March 2015 Accepted 11 March 2015
the uptake of the PET tracer. In fact, for clinically used concentrations of oral contrast agents, phantom measurements showed an overestimation of a 2-deoxy-2-(18F) fluoro-D-glucose (18F-FDG) concentration of ∼ 4–20% [2]. However, the effect of oral CT contrast media seems to be negligible when the contrast agent is distributed homogeneously in the bowel [2], and several reports show that artifacts due to oral agents and intravenous contrast usually injected after a PET scan are easily recognizable [3]. As far as the intravenous contrast agent is concerned, a study reported artifacts in PET/CT scans due to the transient bolus passage of undiluted intravenous contrast agent [4]. Several PET/ceCT protocols have been proposed and consists, for example, of a biphasic or triple-phase injection of contrast media [5,6]. A study has been carried out to investigate whether ceCT attenuation correction could introduce artifacts in PET images. Maximum standardized uptake value has been calculated for different anatomical regions (liver, lung, spleen, etc.) and for the sites of recurrence of cancer. A mild increase in maximum standardized uptake value has been shown, especially in the sites of recurrence, when using ceCT for attenuation correction; nevertheless, the results of this study show that the use of intravenous contrast media does not introduce artifacts that could lead to the detection of a pathological increase of 18F-FDG uptake [7]. In our experience, conducting a three-phase ceCT scan at the end of a whole-body PET/ldCT scan leads to good results in terms of both image quality (fused PET with a ceCT) and diagnostic accuracy [8]. Moreover, the advantage of performing a ceCT at the end of a PET/ldCT is that the ceCT can be avoided in those patients with a negative PET/ldCT or in those with no disease located in parenchymatous organs (see below). The gain in image quality and diagnostic accuracy from a PET/ceCT is ‘balanced’ by a relatively higher radiation exposure due to the performance of a diagnostic CT rather than or in addition to a ldCT. Brix et al. [5] found that, per examination, the effective dose was ∼ 26 millisievert (mSv) for PET/ceCT versus 8.5 mSv for DOI: 10.1097/MNM.0000000000000314
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
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PET/ldCT. The higher radiation exposure from a PET/ceCT is actually the main limitation of this type of scan, especially in young patients (with most of them undergoing very closely spaced PET scans for the followup of hematological malignances). 18
F-FDG is the most widely used PET radiotracer in PET/CT examinations. As for staging, when imaging modalities were being compared (18F-FDG PET/ldCT vs. ceCT), the general trend was to consider PET as being superior to ceCT in the staging of several types of tumors characterized by high avidity of this radiotracer [9, 10]. Hodgkin’s lymphoma and non-Hodgkin’s lymphoma represent a category of diseases in which the use of contrast media in a PET/CT scan for both staging and restaging has been frequently discussed, mainly because of the young age at onset of the disease and the frequency of conducting PET/CT examinations during the clinical course of the disease [11]. Several studies have investigated the diagnostic performance of PET/ldCT as compared with PET/ceCT in staging to establish whether PET/ldCT could suffice in staging or restaging these patients. The superiority of PET in staging is mainly due to the recognition of pathological activity in normal-sized tissues (especially lymph nodes) and in bone marrow, where cortical abnormalities appear late during the development of the disease [8,12]. Other studies on the performance of PET and ceCT in other solid tumors lead to similar conclusions. For head and neck cancers, a recent meta-analysis that summarized the results of over 1400 PET/ldCT scans reported a sensitivity and specificity for PET/ldCT of 85 and 98%, respectively [13]; the superiority of PET/ldCT over morphologic imaging in detecting lymph node involvement is well-known [14]. PET adds significantly to the accuracy of staging of cancer in lymph nodes [15]. The major limitation of ceCT in the assessment of lymph node status across all common cancers is the use of lymph node size as the sole criterion for tumor involvement. Although a short-axis diameter larger than 1 cm and the disappearance of normal features such as hilum representation are considered positive for tumor, cancer cells are often present in lymph nodes smaller than 1 cm. The ability of PET to detect cancer in normal-sized lymph nodes and to more accurately categorize larger nodes has led to an increasing trend to prefer it over CT for nodal staging of many epithelial malignancies, including non-small-cell lung cancer [16], esophageal cancer [17], head and neck cancers [18], and cervical carcinoma [19]. Despite the higher sensitivity, the specificity of PET in assessing locoregional disease extension in a PET/ldCT examination is often limited by several factors such as the physiological uptake of 18F-FDG in normal tissues (muscles, vocal cords, brown fat) and its excretion by salivary glands, which may influence image interpretation and often leads to false-positive findings [20]. Moreover, the absence of contrast media in PET/ldCT severely
limits the distinction between lesions and the cleavage planes affecting the staging of several diseases. Pfannenberg et al. [21] found that 6% of patients with lung cancer could be correctly classified as having T4 tumors only after contrast application; in this study a different management in a significant percentage of patients has been chosen on the basis of the results of ceCT. In fact, the CT performed solely for attenuation correction does not allow the identification of cleavage planes between the primary tumor and contiguous structures such as vessels and the chest wall [21]. Strobel and colleagues investigated the accuracy of PET, PET/ldCT, and PET/ceCT in the identification of resectability in a pool of patients with pancreatic cancer. The exclusion criteria for surgery were the presence of metastasis, peritoneal carcinomatosis, and the infiltration of large vessels or adjacent organs. PET/ceCT has shown a gain in diagnostic accuracy (88%) as compared with PET (70%) and PET/ldCT (76%), as well as in specificity (82 vs. 44 and 56%); in particular, ceCT allowed the detection of liver metastasis and the invasion of large vessels that were not detectable in ldCT [22]. Another limitation of nonenhanced CT is represented by the distinction of the anatomical structures of the abdomen and pelvis where, without the use of contrast media, it is difficult to distinguish the bowel or vessels from adjacent structures, especially after surgery. In a PET/ldCT, the physiological increase in glucose consumption in the bowel and the 18F-FDG excretion in the urinary pathways severely limit the performance of PET in distinguishing physiological from pathological uptake. Hence, it is not surprising that, compared with PET/ldCT, PET/ceCT determined the status of pararectal lymph nodes, internal iliac lymph nodes, and obturator lymph nodes more correctly [23]. The diagnostic accuracy of ceCT versus ldCT in a hybrid PET/CT scan was retrospectively evaluated on 53 patients with colorectal cancer [23]. Lymph node assessment was correctly established by PET/ldCT and PET/ceCT in 70 and 79% of the patients, respectively, with an increase in specificity (42 vs. 68%) [23]. PET has been shown to be inferior to ceCT in the detection of lesions in the liver and the spleen, especially when the dimensions are smaller than 1 cm [8,12,20]. The limitations of diagnostic accuracy of PET in both the spleen and the liver resides in the spatial resolution of PET and, mainly, in movement artifacts due to normal breath, which severely limits the detection of lesions close to respiratory muscles such as the diaphragm [24]. The novel technical advances (i.e. respiratory gating) that have been introduced to avoid these motion artifacts [24], even if effective, are difficult to introduce into common clinical routine because they are often time-consuming. As for restaging, recent studies show that ceCT has a minor role in restaging lymphoproliferative disorders in a PET/CT examination, with the early assessment of
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therapy response being represented by a metabolic rather than a morphological change [11]. Several studies in fact show that the disappearance or persistence of a negligible 18 F-FDG uptake in a site of previous illness location is related to a higher disease-free survival regardless of the dimension of the residual pathological tissue [11]. Differently from hematological malignancies, ceCT changed the therapy approach in 9% of patients who underwent a PET/ldCT and a PET/ceCT examination, with the majority of the lesions missed by PET/ldCT being located in the liver [25]. The authors reported that, compared with PET/ldCT, PET/ceCT revealed additional information in 72% of patients, with a significant impact on therapeutic decisions in 42% [25]. The limitations described previously for the detection of lesions in the liver and the spleen at staging are worsened with the start of chemotherapy (CHT), with the tumor response to CHT being related to a reduced glucose consumption that makes the lesions less detectable in PET [26]. Tan and colleagues demonstrated that, at the level of the liver, cancer cells are detectable in 85% of lesions that show a disappearance of pathological glucose consumption after CHT. This suggests that, even if PET is a sensitive tool for the detection of early response to CHT, the absence of pathological metabolism does not mean a complete response to therapy [27]. Another study has shown significant reduction in 18F-FDG uptake in patients treated preoperatively with CHT, resulting in less efficient detection of cancerous lesions [28]; the sensitivity of PET/ldCT and ceCT in detecting colorectal metastases was significantly higher in CHT-naive patients, whereas ceCT had a higher sensitivity than PET/ldCT in detecting metastases following neoadjuvant therapy (65.3 vs. 49%) [29]. Other authors report an underestimation of 52% of lesions in patients with colorectal cancer who are subjected to a PET/ldCT instead of ceCT during treatment [30]; the sensitivity of PET/ldCT moves from 92 to 63% in those patients treated with CHT before examination [31]. Recently it was shown that an increased glucose consumption in the liver (probably due to toxic CHT effects) results in an increase in background activity [32]and then in difficult interpretation of PET images. Therapeutic treatments and procedures could lead to false-positive findings in PET. It has been reported that, especially after therapy, the inflammatory processes that occur in patients (generally due to surgery or radiotherapy) are a frequent cause of false-positive PET findings, as the activated inflammatory cells show increased 18F-FDG uptake. The conjunction of PET with ceCT could help in the identification of physiological 18F-FDG in normal tissues and, on the other side, the identification of pathological 18F-FDG uptake in tissues with no pathological abnormalities [33].
Several types of tumors are characterized by a low glucose consumption. When 18F-FDG PET is chosen for diagnostic purposes in cancers with a low glucose metabolic rate (i.e. for assessing the transformation of an indolent disease in a more aggressive disease [34]), the conjunction of PET/ldCT with ceCT is essential for correct staging of the disease due to the detection of pathological areas that do not show increased glucose consumption [9,35]. To our knowledge, few studies investigated the added value of ceCT in a PET/CT examination with radiotracers other than 18F-FDG, such as L-3,4-dihydroxy-611 (18F-FDOPA), Cor [18F]fluorophenylalanine 18 68 F-choline, or Ga-DOTA-TOC. These radiolabeled compounds are used, respectively, for the evaluation of primary brain tumors (18F-FDOPA), prostate cancer (11C- or 18F-choline), and neuroendocrine tumors (18F-FDOPA and 68Ga-DOTA-TOC). It is reasonable to suppose that, with few exceptions, the conjunction with a ceCT could be of help in the interpretation of PET data, especially for those anatomical sites characterized by physiological uptake of these radiotracers or where paraphysiological uptake of these compounds could lead to pitfalls in image interpretation [36,37]. As a last aspect, a recent paper investigated the economic impact of PET/ldCT and ceCT in the same examination as compared with the performance of the two imaging modalities at different times [38]. In this paper the authors analyzed the costs for the hospital and for the patients (n = 150), taking into account the direct (technology, physicians, medical staff, etc.), indirect, and social costs (loss of hours of work, travels, etc.). The results show an economic advantage for the protocol that includes the performance of a PET/ldCT and a ceCT in a single session; a significant reduction in the waiting period between the execution of PET/ldCT and ceCT was observed as well, with a significant reduction in the time to diagnosis and to begin the treatment [38]. In conclusion, the use of contrast-medium CT should be recommended for most patients with cancer for whom anatomical details are vital for correct staging of the disease or for surgical planning (i.e. invasion of large vessels or of the adjacent structures) or in the case of cancer location or recurrence in parenchymatous organs. A scrupulous selection of patients is indispensable and should take into account the higher radiation exposure of a diagnostic CT in a PET/CT examination.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
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