PET/CT; State of the art and future prospects

Year 9, Number 36, April 2007

PET/CT; State of the art and future prospects

Vahid Reza Dabbagh Kakhki MD^[1].
^[1]Assisstant Professor, Nuclear Medicine Department, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad , Iran.

Correspondence:

Vahid Reza Dabbagh Kakhki MD
Nuclear Medicine Department, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Tel: 0098-511-8599359
E-MAIL: vrdabbagh@yahoo.com

Cita/Reference:
Dr. Vahid Reza Dabbagh Kakhki .
Assisstant Professor. PET/CT; State of the art and future prospects. Alasbimn Journal 9(36): April 2007. Article N° AJ36-5.

Abstract

Many papers have demonstrated both the relevant impact of positron emission tomography (PET) on staging of many cancers, and the superior accuracy of the technique compared with conventional diagnostic methods for pre-treatment evaluation, therapy response evaluation, and relapse identification. But, PET/CT is a new imaging modality that integrates functional (PET) and structural (CT) information into a single scanning session, thus improving lesion localization and interpretation accuracy. PET/CT fusion images result in higher diagnostic accuracy with fewer equivocal findings. With attenuation correction performed by the CT component, PET/CT can provide higher quality images over shorter examination times than conventional PET. PET/CT is currently the most advanced technique of metabolic imaging and the most accurate tool for tumor staging in the pretreatment, post-treatment and follow-up phases. Although PET/CT offers many advantages, this dual-modality imaging also poses some challenges such as misregistration due to respiration, overattenuation correction due to metals, etc.

Introduction

Positron emission tomography (PET) is one of the fastest growing techniques in nuclear medicine today. Fluoro-deoxyglucose (¹⁸F-FDG) is an analog of glucose and, as such, a versatile radiopharmaceutical with major applications in oncology, neurology, and cardiology. Clinically ¹⁸F-FDG PET is most widely used for cancer detection that tumors were seen as hypermetabolic lesions by an increase in tracer uptake ^1. The availability of various radiotracers labeled with positron emitters currently enables even the quantitative assessment of not only the glucose and protein tissue metabolism but also the extent of enzyme expression, receptor density, the presence and degree of neurotransmitter activity, blood flow, tissue hypoxia and angiogenesis. This enables molecular alterations to be revealed even when structural and morphological changes are unidentifiable or difficult to identify. Many papers have demonstrated both the relevant impact of FDG PET (as a molecular imaging technique enabling early assessment of molecular alterations invivo) on early diagnosis, staging of many cancers and the superior accuracy of the technique compared with conventional diagnostic methods for pre-treatment evaluation, therapy response evaluation and relapse identification. In particular PET was found useful in identifying lymph nodal and metastatic spread, thus altering patient management in more than 30% of cases ^1, 2. PET images show functional information, however they provide limited anatomical data, which in regions such as the head and neck, mediastinum and pelvic cavity is a significant drawback ^2, 3. The exact localization of lesions may also be difficult in some cases on the basis of PET images alone. In many cases, the studies are interpreted with the help of anatomic information in X-ray CT and magnetic resonance (MR) images ^3. However, image fusion is often difficult or impossible, as CT or MR examinations are not always available. When they are, they may have been performed at different times or may not be appropriate for an effective comparison. It should also be borne in mind that even when optimal images are available, complex software is required for image fusion, which creates numerous technical problems and requires anything but short turn-around times. The significant impact of these problems on clinical practice has prompted the manufacturers of imaging devices to develop a hybrid device (PET/CT) consisting of a single patient bed, a high quality PET scanner and a multislice CT device ^4. In the last 2 years, PET imaging in oncology has been migrating from the use of dedicated PET scanners to the use of PET/CT tomographs. According to a recent market study, sales of PET/CT scanners have surpassed those of dedicated PET scanners by 65% since 2003 and sales of PET/CT scanners are anticipated to grow by more than 95% over the next few years ^5.

PET radiotracers

Unstable nuclides which emit positron are used in PET imaging. The positron has the same mass as an orbital electron but is positively charged. A unique characteristic of the positron is that it can not exist at rest in nature. Once it loses its kinetic energy, the positron immediately combines with a negatively charged electron and undergoes annihilation reaction in which the masses of the two particles are completely converted into energy in the form of two 0.511-Mev annihilation photons, which leave their production site at 180 degrees from each other. The coincidence (simultaneous) detection of the two 511-keV gamma rays forms the basis for imaging with PET ^6, 7.

The biologic ubiquity of the elements available as positron emitters gives PET an unprecedented power to image the distribution and kinetics of natural and analog biologic tracers ^8. The most commonly used radiotracer in clinical practice and the study of cancers is FDG labeled with ¹⁸F. The FDG actively fixes at the cellular level thanks to glucose transporters, is phosphorylated and no longer metabolized, and therefore remains trapped within the cell. Positron-emitting radionuclides with a very short half-life, such as oxygen-15, nitrogen-13 and carbon-11, can only be used at the production sites equipped with a cyclotron. ¹⁸F with a relatively longer half-life of about 110 min can instead be distributed from the production site to other centers equipped with only a scanner and which are within two hours traveling distance. Other radiotracers contribute to the study of protein metabolism (¹¹C-methionine, ¹¹C-tyrosine), the extent of cellular proliferation (¹⁸F-fluorothymidine) , the metabolism of membrane phospholipids (¹¹C-choline), hypoxia (¹⁸F-fluo-romisonidazole), apoptosis (¹⁸F-annexin V) and angiogenesis (¹⁸F-rginine-glycine aspartic acid). Tumors take up PET radiotracers more intensely than healthy tissue and are therefore recognizable as areas of increased radioactive concentration ^2.

PET and PET/CT scanners

The most recent PET scanners are made up of a large number of detectors arranged on numerous rings and are able to identify pairs of 511 KeV photons emitted at 180° to each other which are formed following the annihilation of a positron when it meets an electron. These data are converted in tomographic images, with coronal, transaxial and sagittal sections 3-4 mm thick capable of revealing lesions with a diameter of about 4-5 mm ^2.

As the two 511-keV gamma-rays pass through the body, there is likelihood that one or both of the gamma-rays will be absorbed or will be scattered away from the two detectors they would have hit (attenuation). Guaranteeing optimal quality requires the attenuation correction with measuring attenuation correction factors. For this purpose, acquisition of transmission scan and emission images were done.

-Transmission scan: Positioning the patient in the scanner( the patient has not been given an injection of positron emitter at this stage) and acquire scan with activity from the external rod or point source using a radionuclide source of germanium-68 emitting positrons or cesium-137 emitting gamma rays.

-Emission scan: acquire scan from the patient after injection of positron emitter ⁸ .

The acquisition of transmission images enables correction for the attenuation of emission images to be performed. This not only leads to a significant improvement in image quality, but also enables a quantitative analysis of the extent of radiotracer uptake within the tissues to be performed ^{2, 8}.

In a PET/CT scanner, the PET and CT tomographs are housed in a single gantry with a single patient bed and workstation. The CT tomography is usually in the front of gantry, and the PET tomography in the back. PET/CT scanners can be used either as a dedicated PET scanner or as a dedicated CT scanner. The CT scanner can be dual or multislice, with axial or helical acquisition modes and different rotation speeds ^9. One main advantage of a PET/CT scanner is that it uses the CT images(as transmission images) for attenuation correction of the PET data rather than relying on a rotating transmission rod source. PET/CT scanners are able to perform the registration of the transmission images in extremely short times -less than a minute - with the PET study acquisitions performed immediately after. Upon reconstruction, both the PET images and the CT images are displayed side by side and overlaid (fused) ^10. Use of the CT scan reduces the total PET acquisition time which translates into increased patient comfort and therefore increased patient cooperation ^2. In addition, the availability of high quality transmission images enables improved accuracy and precision attenuation correction of the emission images and a more precise localization and interpretation of the hypermetabolic lesions, thanks to the availability of anatomical landmarks ^2, 10.

Challenges with PET/CT

The artifacts most commonly seen on PET/CT images are due to metallic implants, respiratory motion and contrast medium ¹⁰. The coregistration of CT and PET images can produce artifacts not only caused by patient movement, particularly of the head-neck, but also by different breathing conditions during the two acquisitions ^2. The CT images can be acquired with a single breath hold after maximum expiration or after maximum inspiration, whereas during the long acquisition time of a PET scan, the patient breathes freely. The final PET images are hence an average of many breathing cycles. The artifact is due to the discrepancy between the chest positions on the CT and PET images ^11, 12. Artifacts can be reduced, particularly in relation to the regions immediately above and below the diaphragm, by performing the CT scan with a single breath hold after normal expiration. Due to the possible presence of artifacts, a careful and separate examination of the emission and transmission images is advisable ^2.

One problem which still has not been completely solved regards the use of iodinated or barium-containing contrast materials to enable the visualization of the bowel loops, particularly those of the small bowel, and the vascular structures ^13, 14. In this regard it is worth noting that while some PET centers frequently use contrast media, most centers tend to use them only in selected cases and in well defined protocols ^2. High contrast concentrations result in high CT numbers and streaking artifacts on CT images as well as high PET attenuation coefficient, leading to an overestimation of tracer uptake, thereby producing false-positive PET results ^15, 16, 17. Clearly there is a need to establish before the event in which cases oral contrast media should be used, bearing in mind that the media are usually administered in two doses, one immediately before and one 30 min after the radiotracer injection, so as to obtain a satisfactory visualization of the proximal and distal bowel loops ^2.

As already stated the transmission CT images are used for the correction of the attenuation of the PET emission images. There is therefore need to avoid the use of oral contrast media causing artifacts in the correction procedure of the emission images. It has been shown that these artifacts can be completely avoided if very low density oral contrast materials are used (1.2-2.1 vol%). The visualization of the bowel loops is useful only when a PET/CT scanner is used and when those abdominal cancers are studied which give rise to peritoneal diffusion and lymph node involvement, such as ovarian and colon cancer. A more complex issue is the use of intravenous iodinated contrast media, both with regard to the need for close cooperation between the nuclear medicine physician and the radiologist and because the CT scans with contrast medium need to be performed after the PET acquisitions. Clearly then the use of a CT scan with intravenous contrast medium appears justified only in selected cases, when the visualization of the vessels and the perivascular anatomical structures are capable of providing additional useful information for significantly improving the interpretation of the findings, or when a reduction in the radiation dose or avoiding additional anesthesia is involved, as in the case of cancer in pediatric PET/CT ^2.

Metalic implants result in high CT numbers and generate streaking artifact on CT images because of their high photon absorption. This increase in CT numbers results in correspondingly high PET attenuation coefficients, which lead to an overestimation of the PET activity in that region and thereby to a false positive PET findings ^10. As a result, technologists should ask patients to remove all metallic objects before imaging and should document the location of nonremovable metallic objects to minimize or identify such artifacts.

Main indications for PET/CT

There are numerous reports which outline the appropriate indications for FDG PET for pretreatment, post-treatment and follow-up in the study of a variety of cancers ^1, 2. There are, however, no precise indications for the use of PET/CT, since the literature available is relatively limited and refers for the most part to a small number of cases. Nonetheless the literature clearly identifies that PET/CT presents important advantages with respect to PET alone in localizing and interpreting hypermetabolic lesions, especially when they are in anatomically complex body regions and in all cases where normal anatomy has been altered following surgery or radiation therapy ^18, 19. A higher sensitivity and specificity of PET-CT compared with PET alone has been documented in demonstrating recovery from colorectal cancer ^20, ^21, ovarian cancer ²² and non-small-cell lung cancer. Studies comparing PET and PET-CT have shown that PET-CT is capable of providing additional information regarding pretreatment staging of patients with non-small-cell lung cancer, with an improvement in diagnostic accuracy particularly regarding the assessment of the N and M parameters ^23, 24, 25. With regard to esophageal cancer PET and PET-CT ^22, 26 have proven useful in preoperative staging, with a diagnostic accuracy greater than CT in identifying lymph node involvement . The treatment of esophageal cancer, head-neck cancer and rectal cancer often involves neoadjuvant chemoradiotherapy before possible surgery, especially when at diagnosis the cancer presents local-regional diffusion. PET and especially PET/CT ²⁷ are able to assess the extent of treatment response with greater precision, with important consequences for treatment choice and patient prognosis. PET/CT has excellent possibilities in providing more useful information than CT with regard to performing radical radiotherapy, both for modifying treatment in the case of identifying lesions not encountered with conventional imaging techniques and for optimizing treatment plans. In modern conformation radiotherapy the precise definition of the fibrous or necrotic component of the tumor allows for appropriate corrections of the volume to be irradiated ^28. With reference to the data published in the literature the PET/CT study is most appropriate in the following situations:

- staging of tumors situated in anatomically complex body regions (head-neck, mediastinum, pelvic cavity);

- staging of tumors where assessing possible lymph node involvement is particularly important, such as in non-small cell lung cancer in the pretreatment phase or ovarian cancer or colon-rectal cancer where relapse is suspected;

- assessing doubtful and inconclusive CT findings regarding relapse;

- tumors with indications for radical radiotherapy, with the aim of staging and optimizing the treatment plan.

As well as these indications, which may lead to preferential planning for the use of a PET/CT study, unforeseen cases may arise where there is difficulty in localizing and interpreting hypermetabolic lesions. These considerations underline the problem of choice a PET centre equipped with only one scanner must currently face: a centre with two or more scanners, including a PET/CT scanner, may perform several patient beds with the PET/CT scanner at the level where there are interpretative problems regarding the localization of hypermetabolic lesions. A PET centre with a single scanner, which is the most frequent situation, should look to acquiring a PET/CT scanner, which offers clear advantages for the study of numerous tumors and which compensates the greater financial investment with an increase in productivity of 25-30%. Further support for this affirmation is provided by several indications still under study which necessarily require the use of a PET/CT scanner, such as studies with ¹⁸F- FDG of multiple myeloma and with ¹¹C-choline of prostate cancer ^2.

Development prospects for PET/CT

The availability of PET-CT scanners opens up development prospects of metabolic imaging which although yet tobe defined are potentially highly relevant, with the possibility not only of increasing diagnostic accuracy of many indications already recognized as appropriate, but also in tackling problems of diagnostic precision and tumor staging, the study of which has so far proven difficult with PET scanners alone. The new indications, which still require studies on a sufficiently large number of cases in order to define their appropriateness, include the use of PET/CT with ¹¹C-choline in the study of prostate cancer having already undergone treatment and suspected of relapse where conventional imaging findings are dubious or inconclusive ^2. PET/CT can identify bone metastases, even small occurrences in the initial phase, as well as lymph node involvement, even when they are not enlarged, in correspondence with the pelvic cavity or the lumboaortic region. Progress has been made in multiple myeloma regarding treatment possibilities, with an improvement in cure rates or long-term survival. Owing to its ability to study the whole body and precisely locate lesions, PET/CT is able to provide more information than conventional imaging techniques not only in the pretreatment phase, but also post-treatment and in follow-up. PET/CT is able to identify a greater number of bone lesions than conventional radiography examinations, assess whether the bone lesions are in a state of activity and also demonstrate the presence or not of extra-osseous lesions ^29. The PET/CT study which includes all the bone segments is capable of identifying additional lesions and completing the information provided by MR, which in general is limited to the spine and pelvis. Lastly, PET/CT has been recognized as an important technique in the study of plasmacytosis owing to its ability to identify lesion sites other than the one already known. PET/CT is particularly useful in the study of some cancers in the advanced stage or not susceptible to surgery, such as head-neck cancer, esophageal cancer, non-small-cell lung cancer and breast cancer ^23. In these cases neoadjuvant chemoradiotherapy is performed, for which a pre and post-treatment assessment is vital for establishing the metabolic response to therapy. The PET/CT study precedes or at any rate is more sensitive than the simple morphological assessment ^30. The availability of different chemotherapy protocols with different levels of toxicity has emphasized the need for an early assessment of patient response to treatment so as to avoid useless iatrogenic effects affecting non-responsive patients. With its greater accuracy than PET alone, PET/CT can perform a precise and early assessment even of the quantitative type regarding the response to chemotherapy at the level of the individual lesions, especially of malignant lymphomas and breast, ovarian and colon-rectal cancer ^23, 24. In the study of head-neck cancer PET/CT is able to make an early assessment of the effectiveness of radiotherapy, preferably using in this case methionine labeled with ¹¹C, for which unlike for ¹⁸F-FDG there is no uptake by inflammatory foci. PET/CT with ¹¹C-methionine is also capable of performing a more precise assessment of residual or relapse cerebral glioblastomas following surgery or radiotherapy. Although still not fully defined, the use of PET/CT is promising in providing additional useful information for optimizing treatment management in modern conformation radiotherapy, both in its ability to reveal lesion not identified with conventional techniques, which can lead to a modification of either treatment or the size of the fields to be irradiated, and in its precise definition of the fibrous or necrotic component of the tumor, which may lead to the administration of additional dose on well defined areas, thus saving healthy tissue ^2.

Conclusions

PET/CT imaging resolves the limitations of dedicated PET by making use of a rapid low-noise CT scan for attenuation correction, thereby improving image quality while decreasing patient discomfort and increasing patient throughput. PET/CT integrates functional (PET) and structural (CT) information into a single scanning session, improving lesion localization and interpretation accuracy. PET/CT is currently the most advanced technique of metabolic imaging and the most accurate tool for tumor staging in the pretreatment, post-treatment and follow-up phases. Progressive technological development of PET/CT scanners is foreseeable in the near future with an increase in the efficiency of detector crystals, the spatial resolution and a reduction in acquisition times of the emission images. As has already occurred over the past two years, most PET centers tend to acquire PET/CT scanners and an increase in their availability is definitely foreseeable.

References

1.

Gambhir SS, Czernin J, Schwimmer J, et al. A tabulated summary of the FDG PET literature. J Nucl Med 2001;42(supl): 1S-93S. Volver

2.

Fanti S, Franchi R, Batista G, Monetti N, Canini R. PET and PET-CT. State of the art and future prospects. Radiol Med 2005;110:1-15.  Volver

3.

Turkington TG, Bowsher JE. New technologies in nuclear medicine. In: Sandler MP, Coleman RE, Patton JA, Wackers FJTH, Gottschalk A. Diagnostic nuclear medicine. 4^th ed. Philadelphia: Lippincott Williams & Wilkins,2003: 85-93.  Volver

4.

Costa DC, Visvikis D, Crosdale I, et al. Positron emission and computed X-ray tomography: a coming together. Nuc Med Commun 2003; 24: 351-358.  Volver

5.

Czernin J. Schelbert H. PET/CT imaging: facts, opinions, hopes, and questions. J Nucl Med 2004;45(supl):1S.  Volver

6.

Patton JA. Basic physics of nuclear medicine. In: Sandler MP, Coleman RE, Patton JA, Wackers FJTH, Gottschalk A. Diagnostic nuclear medicine. 4^th ed. Philadelphia: Lippincott Williams & Wilkins,2003: 85-93.  Volver

7.

Meikle SR, Dahlbom M. Positron emission tomography. In: Murray IPC, Ell PJ, Van der Wall H, Strauss HW. Nuclear medicine in clinical diagnosis and treatment. 2^nd ed. Edinburg: Churchill Livingstone,1998:1603-1616.  Volver

8.

Cherry SR, Phelps ME. Positron emission tomography: methods and instrumentation. In: Sandler MP, Coleman RE, Patton JA, Wackers FJTH, Gottschalk A. Diagnostic nuclear medicine. 4^th ed. Philadelphia: Lippincott Williams & Wilkins,2003: 61-83.  Volver

9.

Beyer T, Townsend DW, Brun T, et al. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;41:-1369-1379.  Volver

10.

Sureshbabu W, Mawlawi O. PET/CT imaging artifacts. J Nucl Med Technol 2005;33:156-161.  Volver

11.

Osman MM, Cohade C, Nakamoto Y, wahl RL. Respiratory motion artifacts on PET emission images obtained using CT attenuation correction on PET-CT. Eur J Nucl Med Mol Imaging 2003;30:603-606.  Volver

12.

von Schulthess GK, Normal PET and PET/CT body scans: imaging pitfalls and artifacts. In: von-Schulthess GK, ed. Clinical Molecular Anatomic Imaging: PET, PET/CT and SPECT/CT. Baltimore: Lippincott, Williams & Wilkins, 2002:252-270.  Volver

13.

Dizendrof EV, treyer V, Von Schuthess GK, et al. Application of oral contrast media in coregistered positron emission tomography-CT. AJR 2002; 179:477-481.  Volver

14.

Antoch G, Freudenberg LS, Beyer T, et al. To enhance or not enhance? 18F-FDG and CT cntrast agents in dual-modality 18F-FDG PET/CT. J Nucl Med 2004;45:56S-65S.  Volver

15.

Antoch G, Freudenberg LS, Egelhof T, et al. Focal tracer uptake: a potential artifact in contrast-enhanced dual-modality PET/CT scans. J Nucl Med 2002;43:1339-1342.  Volver

16.

Cohade C, Osman M, Nakamato Y, et al. Initial experience with oral contrast in PET/CT: phantom and clinical studies. J Nucl Med 2003; 44:412-416.  Volver

17.

Dizendorf E, Hany TF, Buck A, von Schulthess GK, Burger C. Cause and magnitude of the error induced by oral CT contrast in CT-based attenuation correction of PET emission studies. J Nucl Med 2003; 44: 732-738.  Volver

18.

Schoeder H, Erdi YE, Larso SM, et al. PET/CT: a new imaging technology in nuclear medicine. Eur J Nucl Med Mol Imaging 2003;30:1419-1437.

19.

Bar-shalom R, Yefremov N, Guralnik L, et al. Clinical performance of PET/CT in evaluation of cancer: additional value for diagnostic imaging and patient management. J Nucl Med 2003;44: 1200-1209.  Volver

20.

burger I, Goerres G, von Schulthess GK,et al. PET/CT: diagnostic improvement in recurrent colorectal carcinoma compared to PET alone. Radiology 2002;225:224.

21

. Cohade S, Osman M, Leal J, et al. Direct comparison of 18F-FDG PET and PET/CT in patients with colorectal carcinoma. J Nucl Med 2003;44:1793-1803.  Volver

22.

Dehdashti F, Siegel BA. Neoplasm of the esophagus and stomach. Seminars Nucl Med 2004; 34: 198-208.  Volver

23.

Abouzied MM, Crawford ES, Nabi HA. 18F-FDG imaging: pitfalls and artifacts. J Nucl Med Technol 2005; 33:145-155.  Volver

24.

Goerres GW, Kamel E, Seifert B, et al. Accuracy of image coregistration of pulmonary lesions in patients with non small-cell lung cancer using an integrated PET-CT system. J Nucl Med 2002;43:1469-1475.  Volver

25.

Lardinois D, Weder W, Hany TF, et al. Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography. N Engl J Med 2003;348:2500-2507.  Volver

26.

Downey RJ, Akhurst T, Ilson D, et al. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 2003; 21:428-432.  Volver

27.

Kostakoglu L, Goldsmith SJ. PET in the assessment of therapy response in patients with carcinoma of the head and neck and of the esophagus. J Nucl Med 2004; 45: 56-58.  Volver

28.

Dizendorf EV, Baumert BG, von Schulthess GK, et al. Impact of whole body 18F-FDG PET on staging and managing for radiation therapy. J Nulc Med 2003; 44: 24-29.  Volver

29.

Fanti S, Yu JQ, Morreti A, et al. assessment of disease activity in multiple myeloma with FDG-PET imaging. Eur J Nulc Med Mol Imaging 2004; 31(suppl 2) S 286.  Volver

30.

Kostakoglu L, Goldmith SJ. 18F-FDG PET evaluation for lymphoma and for breast, lung and colorectal carcinoma. J Nucl Med 2003;44:224-239.  Volver

Sitio desarrollado por SISIB - Universidad de Chile