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Commentary: Ahead of the Curve |

Future of Thoracic PET ScanningFuture of Thoracic PET Scanning FREE TO VIEW

Geoffrey B. Johnson, MD, PhD; Patrick J. Peller, MD; Bradley J. Kemp, PhD; Jay H. Ryu, MD, FCCP
Author and Funding Information

From the Department of Radiology (Drs Johnson, Peller, and Kemp), the Department of Immunology (Dr Johnson), and the Division of Pulmonary and Critical Care Medicine (Dr Ryu), Mayo Clinic, Rochester, MN.

CORRESPONDENCE TO: Geoffrey B. Johnson, MD, PhD, Department of Radiology, Mayo Clinic, 200 1st St SW, Rochester, MN 55905; e-mail: johnson.geoffrey@mayo.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(1):25-30. doi:10.1378/chest.14-1612
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Published online

The advances in PET scanning for thoracic diseases that are deemed most likely to have clinical impact in the near-term future are highlighted in this article. We predict that the current practice of medicine will continue to embrace the power of molecular imaging and specifically PET scanning. 18F-fluorodeoxyglucose-PET scanning will continue to evolve and will expand into imaging of inflammatory disorders. New clinically available PET scan radiotracers, such as PET scan versions of octreotide and amyloid imaging agents, will expand PET imaging into different disease processes. Major improvements in thoracic PET/CT imaging technology will become available, including fully digital silicone photomultipliers and Bayesian penalized likelihood image reconstruction. These will result in significant improvements in image quality, improving the evaluation of smaller lung nodules and metastases and allowing better prediction of prognosis. The birth of clinical PET/MRI scan will add new imaging opportunities, such as better PET imaging of pleural diseases currently obscured by complex patient motion.

Figures in this Article

PET scanning offers better resolution than other nuclear imaging techniques. Unlike nonnuclear molecular imaging techniques, PET scans can identify truly trace amounts of an imaging agent so as to not upset the pathway being imaged. The clinical benefit of this imaging on patient care is clear, changing the care plan of > 30% of patients with cancer.1 This has resulted in exponential growth of PET scanning, and heavy investment in continued improvement.

The current practice of 18F-fluorodeoxyglucose (FDG)-PET/CT scanning for non-small cell lung cancer is expanding into the realm of chemotherapy monitoring. Lack of a rapid and dramatic decrease in FDG activity early in a course of chemotherapy suggests that the therapy is unlikely to result in long-term benefit.2 Thus, therapy decisions do not have to wait until anatomic imaging shows a change in the volume of a given cancer.

In addition to therapy monitoring, improved FDG-PET scan-based prognostic measures are likely to outperform the maximum standard uptake value. Unlike the maximum standard uptake value, which measures the hottest pixel in a tumor, these new measures reflect the total cancer burden, such as metabolic tumor volume or total lesion glycolysis (Fig 1). Metabolic tumor volume and total lesion glycolysis have the potential to rival grade and stage as independent predictors of long-term outcome in patients with non-small cell lung cancer.35 What is needed is wide adoption of better and standardized software for rapid calculation of these metrics.

Figure Jump LinkFigure 1 –  A, B, Quantitative measurements of tumor burden. Patient A and B have a similar tumor type, grade, stage, and SUVmax. However, they have very different tumor burden, and the MTV and TLG predict a worse prognosis for patient A (each panel has maximum intensity projection [MIP] images, axial PET scan, and axial PET/CT scan with automated volumetric regions of interest drawn around sites of malignancy based on a standard uptake value threshold). MTV = metabolic tumor volume; Sq = squamous; SUVmax = maximum standard uptake value; TLG = total lesion glycolysis.Grahic Jump Location

FDG-PET/CT scanning has a role to play in nonmalignant chest diseases, such as active granulomatous infection and inflammation. Despite ongoing research supporting the use of FDG-PET scans for inflammatory conditions, the current lack of Center for Medicare and Medicaid Services (CMS) reimbursement has limited its impact. However, there is a growing movement for considering new and improved FDG-PET/CT scan strategies for the imaging of active systemic inflammatory conditions.

Several inflammatory conditions affect the chest, and the inflammation they cause can be detected by FDG-PET/CT scans (Table 1). These conditions include granulomatous infections, giant cell arteritis, fibrosing mediastinitis, IgG4-related disease (formerly autoimmune pancreatitis), organizing pneumonia, granulomatosis with polyangiitis, and histiocytic processes (eg, Erdheim-Chester disease). These conditions are commonly thought of as pitfalls, referring to real pathology that can mimic the appearance of cancer on FDG-PET scans, and are known for leading to inaccurate interpretations and subsequent inappropriate interventions. On occasion, one has the pleasure of accurately pinpointing one of these conditions based on the PET/CT imaging alone (Table 1). Diagnosing inflammatory conditions is often a result of careful comparison with prior imaging, and the systemic pattern of activity (Fig 2). Knowledge of suggestive patterns of activity seen with inflammatory diseases such as IgG4-related disease, granulomatosis with polyangiitis (Wegener), or sarcoidosis is critical. Perhaps the major impact of FDG PET/CT scanning for patients with these conditions is not the diagnosis, but the posttherapy follow-up.

Table Graphic Jump Location
TABLE 1 ]  PET Scan Patterns in Systemic Inflammatory Conditions
a 

Renal and brain imaging findings should be common in granulomatosis with polyangiitis, but the high background of 18F-fluorodeoxyglucose activity in these organs makes disease involvement difficult to detect in these locations on PET/CT scans.

Figure Jump LinkFigure 2 –  A, B, Use of 18F-fluorodeoxyglucose (FDG)-PET/CT scanning for inflammatory conditions. Images show a systemic pattern of inflammatory FDG activity that suggests IgG4-related disease (IgG4-RD aka autoimmune pancreatitis) and not cancer (axial fused PET/CT scan [A] and MIP image [B]). In this 72-y-old man, there is biopsy-proven IgG4-RD in the salivary glands, pancreas, periaortic retroperitoneum, and prostate. In any one location, the FDG activity does not help differentiate cancer from inflammatory IgG4-RD. FDG-PET/CT scanning is not currently approved by the Center for Medicare and Medicaid Services for the evaluation of known inflammatory conditions. However, these conditions can be identified on FDG-PET/CT scans in patients suspected of having cancer. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

In the setting of suspected active granulomatous inflammation/infection, the advantages of FDG-PET/CT scanning over other imaging modalities include (1) the ability to image otherwise normal anatomic structures affected by inflammation and, thus, increase sensitivity (hotly debated), such as a draining lymph node; (2) the ability to assess response based on the activity of these conditions before and after therapy (limited data, but promising); (3) proper “staging” of the systemic appearance of the condition; and (4) the ability to direct biopsy to the target of lowest risk and/or highest yield. All these points will require further clinical investigation, but have the potential to result in better clinical management of these complicated patients.

In 2012, the US Food and Drug Administration (FDA) took over the active regulation of PET scan radiopharmaceutical (radiotracers used in PET imaging) production. The FDA classifies radiopharmaceuticals as drugs. There was fear that a higher level of regulatory oversight would lead to ever-increasing hurdles for the much-needed new PET imaging agents. However, there have been a handful of approvals in recent years and perhaps a change in tone that suggests the FDA understands both the need for these new agents and the low risk associated with what are often low toxicity profiles. There are two main sources of these upcoming PET scan radiotracers: the conversion of old tried and true planar/single photon emission CT (SPECT) imaging agents and the emergence of completely new classes of agents.

The conversion of planar/SPECT imaging agents to PET imaging agents will allow for far better clinical management of several thoracic diseases, including neuroendocrine tumors such as carcinoid (Fig 3). Octreotide imaging, even with the addition of SPECT/CT scanning, leaves much to be desired in terms of resolution and sensitivity (ie, small tumors do not light up). Carcinoid tumors are poorly evaluated with FDG-PET scans, leaving few good options to properly diagnose small nodules, plan for octreotide therapy, and stage and monitor response to therapy. There is a strong push to bring to the United States octreotide-related PET scan agents, such as 68Ga-DOTANOC6 and 68Ga-DOTATATE,7 which have been well studied across Europe, and we predict that these efforts will be successful within the next few years.818F-DOPA is a neurotransmitter precursor that shows good promise in imaging Parkinson disease. Therefore, 18F-DOPA may be ripe for testing off-label in thoracic diseases and may play a role in imaging neuroendocrine tumors, such as medullary thyroid cancer.9, 10

Figure Jump LinkFigure 3 –  New PET scan radiotracers will open up new imaging opportunities. Here is an example of metastatic carcinoid imaged with 68Ga-DOTATATE PET/CT scan (showing a MIP image, axial PET scan, axial PET/CT scan, and enhanced axial diagnostic CT scan with arrows on liver metastases of different sizes). This is an octreotide analog that can be used with higher-resolution PET/CT imaging rather than 111In-octreotide single photon emission CT/CT scanning. As seen here, metastases in the liver as small as 4 mm can be seen above background. For the evaluation of small FDG-PET/CT scan-negative lung nodules and staging of carcinoid, 68Ga-DOTATATE and 68Ga-DOTANOC have great promise. These imaging agents are not yet approved by the Food and Drug Administration. See Figure 1 and 2 legends for expansion of abbreviations.Grahic Jump Location

18F-FDG-PET bone scans are now approved by the FDA as long as a patient is entered into a national database. Eventually, these scans may replace conventional bone scans. 18F-FDG-PET bone scans have much higher sensitivity for skeletal metastases and take much less time to perform than do conventional bone scans.11 Radiation exposure is similar to that of conventional bone scans.

Several drugs in a new class of PET scan radiotracers related to the old pathologic stain, thioflavin-T, are now approved by the FDA for imaging for the presence of β-amyloid in the brain related to Alzheimer disease. These agents include florbetapir, flutemetamol, and florbetaben. Unfortunately, CMS has approved this class of radiotracers only for imaging patients enrolled in FDA-approved clinical trials and they are, therefore, not yet widely used clinically. Based on preliminary data, and data with PiB (a similar research PET imaging agent), there may be a role for these agents in imaging amyloidoses of the heart and perhaps other organ systems.12

18F-flurpiridaz is in phase 2 clinical trials for myocardial perfusion imaging and may soon become clinically available as a PET scan perfusion radiotracer. Although this article is focused predominantly on lung imaging, the authors would be remiss in leaving out this potential game-changing radiotracer for cardiac perfusion PET imaging. 82Rb is the only widely available PET scan perfusion agent, but it generates lower-resolution images. In centers close to a cyclotron, 13N-ammonia can be used for PET scan blood flow studies. However, flurpiridaz appears to have better imaging characteristics than both rubidium and ammonia and has a 2-h half-life, which allows shipment of this radiotracer to imaging centers. Thus, flurpiridaz is commercially viable and arguably creates better images than other cardiac blood flow agents in nuclear medicine.

A little background before we explain two exciting technologic advances: When PET scan radiotracers are injected into a vein, they travel in the body and emit positrons, a form of antimatter. A positron collides with a nearby electron and the two annihilate each other, becoming pure energy. This energy is emitted in the form of two photons that radiate out to the PET scan camera in opposite directions. It is this pairing of photons that is the key to the superior resolution of PET imaging. Generations of advances in PET scan technology include two-dimensional, three-dimensional, and then time-of-flight (ToF) imaging. With ToF-PET scanners, the crystal detectors, photomultiplier tubes, and electronics are so fast that they can detect which photon hit the detector ring first, and, thus, identify more accurately where the photons came from. Each of these advances required at least an order of magnitude increase in computing power to reconstruct the images in time for a busy clinical schedule.

The next major advances in PET imaging technology arise from two main technologic fronts: (1) new detector systems and (2) postprocessing algorithms. These technologies allow for the more accurate estimation of activity in ever-smaller foci of disease (ie, ever smaller nodules and everything else can be more accurately evaluated).

The next wave of PET scan detector systems was forced into development in anticipation of PET/MRI scanners (a topic to be discussed subsequently). The standard photomultiplier tube-based image detectors fail in an MRI magnet. Solid-state digital PET scan detector systems, such as avalanche photodiodes and more recently silicone photomultipliers (SiPMs), are able to function within magnetic fields. One exciting aspect of these new detector systems is that they promise to significantly improve fundamental imaging parameters such as resolution, regardless of whether they are used in PET/MRI scanners or PET/CT scanners.13 Avalanche photodiodes do not yet allow for high-quality ToF scanning, and therefore, excitement is rising for the adoption of SiPMs. Unfortunately, SiPMs are currently expensive to produce.

An old idea has now led to a new advance in the mathematics used to create PET scan images will have a major impact on PET scan resolution and reproducibility.14 Iterative reconstruction algorithms are the current best mathematical method for creating a PET image from the photon data a PET scan camera collects. Basically, the algorithms use data to create an image and then test that image for accuracy based on other imaging data and certain assumptions about what the image should look like; the process then repeats or iterates. More iterations increase resolution, but they also increase background noise. Previously, many would consider a 7-to-8-mm nodule the lower limit of evaluation with modern PET scan cameras capable of processing ToF data. ToF adds improved resolution to standard 3D iterative reconstruction by taking advantage of faster PET scan detectors and imaging components and differentiating between which photon in each pair hit the detector crystal first. New algorithms, such as Bayesian penalized likelihood algorithms, do not increase background noise, thus allowing many more iterations, and thus much higher resolution in the resulting PET images (Fig 4). Resolution is critical and allows for better evaluation of smaller structures, such as lung nodules. As with all new technologies, penalized likelihood-reconstructed PET images create new artifacts and will require clinical experience.

Figure Jump LinkFigure 4 –  A-C, Recent advances in image reconstruction result in improved PET image resolution. Recently, Food and Drug Administration-approved image processing with Bayesian PL (A) iterative reconstruction shows more accurate measurement of metabolic activity of a 5-mm metastatic nodule than current state-of-the art ToF (B) and older 3D reconstruction (C). With PL, the 5-mm nodule is clearly more active than the mediastinal blood pool in this patient with many liver and lung metastases (A shows FDG-PET scan MIP with arrow on the 5-mm nodule, axial PET scan, and axial PET/CT scan). PL = penalized likelihood; SUVm = maximum standard uptake value; ToF = time of flight. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

Clinical PET/MRI scan has arrived, and tremendous efforts are underway to determine how best to use it.15 The CMS has put out recent statements that oncologic FDG-PET scanning will be reimbursed for the same indications regardless of whether a patient is imaged on PET scan, PET/CT scan, or PET/MRI scan. Although PET/MRI scan is currently still used primarily in research, the new generation of PET/MRI scanners is ready for clinical practice. Of the many hurdles that remain, the major ones revolve around the high cost of the scanners and the difficulty in generating accurate attenuation correction from the MRI images.

Unlike CT scans, MRI images do not reflect the density of tissues being imaged, and therefore are not easily used for attenuation correction. When photons move through tissues, some are blocked, never reaching the PET scan camera’s detectors. Therefore, PET images have to be “corrected” for this loss of photons using an attenuation or density map (such as a CT scan). In PET/MRI scan, there is no such density map. Currently, certain MRI sequences are used to act as a pseudoattenuation correction map, and arguably result in sufficient-quality PET imaging for clinical use.16 Unfortunately, lung tissue is an area where PET/MRI scan attenuation correction may have more difficulty. Thus, the ability to directly compare activity seen on PET/MRI scan with prior or subsequent scans done on the more common PET/CT scanners will need to be evaluated carefully.

MRI of the lungs is in its infancy by comparison with cardiac, spine, musculoskeletal, and brain imaging in terms of the numbers of patients scanned. However, the usefulness of MRI of the chest is rapidly expanding beyond the mediastinum, and MRI protocols and scanners continue to improve their usefulness in thoracic imaging. One potential major advantage of PET/MRI scan is the ability to image a patient simultaneously with both PET scanning and MRI, as opposed to CT scanning followed by PET scanning (hoping the patient does not move between the two scans). PET/MRI scan promises the ability to deconvolute complex tissue movement in the chest and thus greatly improve PET scan resolution, especially around the diaphragm and mediastinal pleura. The authors are anxious to see if these advantages can bear fruit in areas where imaging currently struggles, such as in the evaluation of the pleural spread of lung cancer.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

CMS

Center for Medicare and Medicaid Services

FDA

US Food and Drug Administration

FDG

18F-fluorodeoxyglucose

SiPM

silicone photomultiplier

SPECT

single photon emission CT

ToF

time-of-flight

Hillner BE, Siegel BA, Hanna L, et al. Impact of18F-FDG PET used after initial treatment of cancer: comparison of the National Oncologic PET Registry 2006 and 2009 cohorts. J Nucl Med. 2012;53(5):831-837. [CrossRef] [PubMed]
 
de Langen AJ, van den Boogaart V, Lubberink M, et al. Monitoring response to antiangiogenic therapy in non-small cell lung cancer using imaging markers derived from PET and dynamic contrast-enhanced MRI. J Nucl Med. 2011;52(1):48-55. [CrossRef] [PubMed]
 
Satoh Y, Onishi H, Nambu A, Araki T. Volume-based parameters measured by using FDG PET/CT in patients with stage I NSCLC treated with stereotactic body radiation therapy: prognostic value. Radiology. 2014;270(1):275-281. [CrossRef] [PubMed]
 
Hyun SH, Ahn HK, Kim H, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):50-58. [CrossRef] [PubMed]
 
Davison J, Mercier G, Russo G, Subramaniam RM. PET-based primary tumor volumetric parameters and survival of patients with non-small cell lung carcinoma. AJR Am J Roentgenol. 2013;200(3):635-640. [CrossRef] [PubMed]
 
Ambrosini V, Castellucci P, Rubello D, et al. 68Ga-DOTA-NOC: a new PET tracer for evaluating patients with bronchial carcinoid. Nucl Med Commun. 2009;30(4):281-286. [CrossRef] [PubMed]
 
Kroiss A, Putzer D, Decristoforo C, et al. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT. Eur J Nucl Med Mol Imaging. 2013;40(4):514-523. [CrossRef] [PubMed]
 
Kumar R, Jindal T, Kumar A, Dutta R. (68)Ga-DOTA-TOC/NOC in bronchial carcinoids. Nucl Med Commun. 2009;30(10):822. [CrossRef] [PubMed]
 
Ambrosini V, Marzola MC, Rubello D, Fanti S. (68)Ga-somatostatin analogues PET and (18)F-DOPA PET in medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2010;37(1):46-48. [CrossRef] [PubMed]
 
Marzola MC, Pelizzo MR, Ferdeghini M, et al. Dual PET/CT with (18)F-DOPA and (18)F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: comparison with conventional imaging. Eur J Surg Oncol. 2010;36(4):414-421. [CrossRef] [PubMed]
 
Pisarska B, Kaczmarek A, Smolen M, Kazmierska J, Cholewinski W. Comparison of18F-FDG-PET/CT and99mTc-MDP bone scan in detection of metastatic bone disease. Eur J Nucl Med Mol Imaging. 2012;39(suppl 2):S613-S613.
 
Vedin O, Wikstrom G, Antoni G, et al. [11C]PIB and [11C]Acetate in positron emission tomography: a new method to diagnose and evaluate cardiac function in. patients with cardiac amyloidosis. Circulation. 2010;122(21):A15700.
 
Schaart DR, van Dam HT, Seifert S, et al. A novel, SiPM-array-based, monolithic scintillator detector for PET. Phys Med Biol. 2009;54(11):3501-3512. [CrossRef] [PubMed]
 
Mumcuoglu EU, Leahy R, Cherry SR, Zhou Z. Fast gradient-based methods for Bayesian reconstruction of transmission and emission PET images. IEEE Trans Med Imaging. 1994;13(4):687-701. [CrossRef] [PubMed]
 
Yoon SH, Goo JM, Lee SM, Park CM, Seo HJ, Cheon GJ. Positron emission tomography/magnetic resonance imaging evaluation of lung cancer: current status and future prospects. J Thorac Imaging. 2014;29(1):4-16. [CrossRef] [PubMed]
 
Heusch P, Buchbender C, Beiderwellen K, et al. Standardized uptake values for [¹⁸F] FDG in normal organ tissues: comparison of whole-body PET/CT and PET/MRI. Eur J Radiol. 2013;82(5):870-876. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  A, B, Quantitative measurements of tumor burden. Patient A and B have a similar tumor type, grade, stage, and SUVmax. However, they have very different tumor burden, and the MTV and TLG predict a worse prognosis for patient A (each panel has maximum intensity projection [MIP] images, axial PET scan, and axial PET/CT scan with automated volumetric regions of interest drawn around sites of malignancy based on a standard uptake value threshold). MTV = metabolic tumor volume; Sq = squamous; SUVmax = maximum standard uptake value; TLG = total lesion glycolysis.Grahic Jump Location
Figure Jump LinkFigure 2 –  A, B, Use of 18F-fluorodeoxyglucose (FDG)-PET/CT scanning for inflammatory conditions. Images show a systemic pattern of inflammatory FDG activity that suggests IgG4-related disease (IgG4-RD aka autoimmune pancreatitis) and not cancer (axial fused PET/CT scan [A] and MIP image [B]). In this 72-y-old man, there is biopsy-proven IgG4-RD in the salivary glands, pancreas, periaortic retroperitoneum, and prostate. In any one location, the FDG activity does not help differentiate cancer from inflammatory IgG4-RD. FDG-PET/CT scanning is not currently approved by the Center for Medicare and Medicaid Services for the evaluation of known inflammatory conditions. However, these conditions can be identified on FDG-PET/CT scans in patients suspected of having cancer. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 3 –  New PET scan radiotracers will open up new imaging opportunities. Here is an example of metastatic carcinoid imaged with 68Ga-DOTATATE PET/CT scan (showing a MIP image, axial PET scan, axial PET/CT scan, and enhanced axial diagnostic CT scan with arrows on liver metastases of different sizes). This is an octreotide analog that can be used with higher-resolution PET/CT imaging rather than 111In-octreotide single photon emission CT/CT scanning. As seen here, metastases in the liver as small as 4 mm can be seen above background. For the evaluation of small FDG-PET/CT scan-negative lung nodules and staging of carcinoid, 68Ga-DOTATATE and 68Ga-DOTANOC have great promise. These imaging agents are not yet approved by the Food and Drug Administration. See Figure 1 and 2 legends for expansion of abbreviations.Grahic Jump Location
Figure Jump LinkFigure 4 –  A-C, Recent advances in image reconstruction result in improved PET image resolution. Recently, Food and Drug Administration-approved image processing with Bayesian PL (A) iterative reconstruction shows more accurate measurement of metabolic activity of a 5-mm metastatic nodule than current state-of-the art ToF (B) and older 3D reconstruction (C). With PL, the 5-mm nodule is clearly more active than the mediastinal blood pool in this patient with many liver and lung metastases (A shows FDG-PET scan MIP with arrow on the 5-mm nodule, axial PET scan, and axial PET/CT scan). PL = penalized likelihood; SUVm = maximum standard uptake value; ToF = time of flight. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  PET Scan Patterns in Systemic Inflammatory Conditions
a 

Renal and brain imaging findings should be common in granulomatosis with polyangiitis, but the high background of 18F-fluorodeoxyglucose activity in these organs makes disease involvement difficult to detect in these locations on PET/CT scans.

References

Hillner BE, Siegel BA, Hanna L, et al. Impact of18F-FDG PET used after initial treatment of cancer: comparison of the National Oncologic PET Registry 2006 and 2009 cohorts. J Nucl Med. 2012;53(5):831-837. [CrossRef] [PubMed]
 
de Langen AJ, van den Boogaart V, Lubberink M, et al. Monitoring response to antiangiogenic therapy in non-small cell lung cancer using imaging markers derived from PET and dynamic contrast-enhanced MRI. J Nucl Med. 2011;52(1):48-55. [CrossRef] [PubMed]
 
Satoh Y, Onishi H, Nambu A, Araki T. Volume-based parameters measured by using FDG PET/CT in patients with stage I NSCLC treated with stereotactic body radiation therapy: prognostic value. Radiology. 2014;270(1):275-281. [CrossRef] [PubMed]
 
Hyun SH, Ahn HK, Kim H, et al. Volume-based assessment by (18)F-FDG PET/CT predicts survival in patients with stage III non-small-cell lung cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):50-58. [CrossRef] [PubMed]
 
Davison J, Mercier G, Russo G, Subramaniam RM. PET-based primary tumor volumetric parameters and survival of patients with non-small cell lung carcinoma. AJR Am J Roentgenol. 2013;200(3):635-640. [CrossRef] [PubMed]
 
Ambrosini V, Castellucci P, Rubello D, et al. 68Ga-DOTA-NOC: a new PET tracer for evaluating patients with bronchial carcinoid. Nucl Med Commun. 2009;30(4):281-286. [CrossRef] [PubMed]
 
Kroiss A, Putzer D, Decristoforo C, et al. 68Ga-DOTA-TOC uptake in neuroendocrine tumour and healthy tissue: differentiation of physiological uptake and pathological processes in PET/CT. Eur J Nucl Med Mol Imaging. 2013;40(4):514-523. [CrossRef] [PubMed]
 
Kumar R, Jindal T, Kumar A, Dutta R. (68)Ga-DOTA-TOC/NOC in bronchial carcinoids. Nucl Med Commun. 2009;30(10):822. [CrossRef] [PubMed]
 
Ambrosini V, Marzola MC, Rubello D, Fanti S. (68)Ga-somatostatin analogues PET and (18)F-DOPA PET in medullary thyroid carcinoma. Eur J Nucl Med Mol Imaging. 2010;37(1):46-48. [CrossRef] [PubMed]
 
Marzola MC, Pelizzo MR, Ferdeghini M, et al. Dual PET/CT with (18)F-DOPA and (18)F-FDG in metastatic medullary thyroid carcinoma and rapidly increasing calcitonin levels: comparison with conventional imaging. Eur J Surg Oncol. 2010;36(4):414-421. [CrossRef] [PubMed]
 
Pisarska B, Kaczmarek A, Smolen M, Kazmierska J, Cholewinski W. Comparison of18F-FDG-PET/CT and99mTc-MDP bone scan in detection of metastatic bone disease. Eur J Nucl Med Mol Imaging. 2012;39(suppl 2):S613-S613.
 
Vedin O, Wikstrom G, Antoni G, et al. [11C]PIB and [11C]Acetate in positron emission tomography: a new method to diagnose and evaluate cardiac function in. patients with cardiac amyloidosis. Circulation. 2010;122(21):A15700.
 
Schaart DR, van Dam HT, Seifert S, et al. A novel, SiPM-array-based, monolithic scintillator detector for PET. Phys Med Biol. 2009;54(11):3501-3512. [CrossRef] [PubMed]
 
Mumcuoglu EU, Leahy R, Cherry SR, Zhou Z. Fast gradient-based methods for Bayesian reconstruction of transmission and emission PET images. IEEE Trans Med Imaging. 1994;13(4):687-701. [CrossRef] [PubMed]
 
Yoon SH, Goo JM, Lee SM, Park CM, Seo HJ, Cheon GJ. Positron emission tomography/magnetic resonance imaging evaluation of lung cancer: current status and future prospects. J Thorac Imaging. 2014;29(1):4-16. [CrossRef] [PubMed]
 
Heusch P, Buchbender C, Beiderwellen K, et al. Standardized uptake values for [¹⁸F] FDG in normal organ tissues: comparison of whole-body PET/CT and PET/MRI. Eur J Radiol. 2013;82(5):870-876. [CrossRef] [PubMed]
 
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