The Use of PET Scans in Otolaryngology
Larry Simon, M.D.
May 5, 2005

Our case presentation today deals with a 57-year-old Caucasian woman who presented to an outside oral surgeon for evaluation of a hard palate lesion that she has had for about two to three years. She had no history of tobacco consumption or any significant risk factors for a head and neck malignancy, and she was diagnosed with a torus palatini and followed clinically. However, the lesion progressed and developed with a central area of ulceration and became very painful and caused difficulty with speech and swallowing. In July in 2004, the oral surgeon locally excised it. This did not resolve the problem, however, and during the healing process, it developed another non-healing oral ulcer. This ulcer was then biopsied, and the biopsy revealed a well-differentiated squamous cell carcinoma. The patient was then referred to Baylor College of Medicine for further evaluation and upon our initial assessment we found a 2 cm ulcerative lesion on the hard palate and a firm level II lymph node. There was no other lymphadenopathy. Her cranial nerves were all intact. There were no other abnormalities on physical exam.

As part of the work-up for this, the patient received a PET CT. The CT portion of this evaluation is shown here, and you can see clearly a grouped level of upper jugular chain lymph nodes. On PET imaging, these lymph nodes showed very high uptake of tracer. This is very concerning for metastatic disease and, indeed, affected the patient’s surgical treatment. She received a partial palatectomy as well as a supraomohyoid neck dissection on the left, and three of eight lymph nodes were found to be positive, including this lymph node that was identified on the PET scan.

PET scans were invented in the 1950s by Drs. Brownell and Sweet at Massachusetts General Hospital. Their initial use was to study brain function. Initially there was not much effort put into their use for clinical applications. The first application in head and neck cancer was done in 1988. The key breakthrough for PET came in ’97 and ’98 when it received approval by the FDA and by the CHFA for Medicare reimbursement. Since then, it has become a widely used clinical tool for the evaluation of head and neck cancer.

PET scan is based on principles of nuclear decay. Whereas computed tomography and magnetic resonance imaging are based on absorption of different particles by radiation administered to them, positron emission tomography is based on nuclear decay and radiation emitted by the patient. The cyclotron, shown here, bombards a normal isotope of an element with protons. This creates an unstable isotope plus a neutron. This is the form in which it is administered to the patient—the unstable isotope with the neutron. In the patient, this unstable isotope undergoes nuclear decay and reverts back to the normal isotope. In this process, it emits a positron. One example of this is the use of oxygen. Oxygen’s normal mass number is 16—8 protons and 8 electrons—but it can carry an extra two neutrons and have a mass number of 18. If you bombard this element with protons, one of them will stick, and you will go from a nuclear number of 8 to 9, creating flourene. However, when you have nine protons, you still only have 8 electrons. It is very unstable. Eventually, this element will decay and release a proton, reverting back to 18 oxygen. This proton decays into a positron, a neutrino, and a neutron. The positron emission is what is detected.

So, the positron is floating around and is going to run into an electron. They undergo an annihilation reaction that releases gamma radiation and this gamma radiation is what is actually detected in positron emission tomography. Some very complicated mathematics are used to transform this energy gamma irradiation into a three A number of isotopes can be used. Here is a selection: bromide, carbon, fluorine, and oxygen. Fluorine has the longest half life. Cyclotrons are very large, expensive, and cumbersome instruments. The advantage of the long half-life of fluorene is that you can generate the radioactive isotope at an outside facility and then administer it at your hospital and use your positron emission scanner. You do not need to have an on-site cyclotron when you are using isotopes with longer half lives.

In positron emission tomography versus traditional imaging, we are actually imaging cell physiology; we are not imaging anatomy. The goal is to identify neoplastic tissue. If we think about what separates cancer cells from benign cells, one of the keys is a very high metabolic rate. They have overexpression of glute-1 through glute-6, and as a result, have increased glucose uptake. If we use radiolabeled glucose, we can convince these neoplastic cells to emit radiation, allowing us to see them. If you take a normal glucose molecule and transform one of its oxygens into an 18 oxygen, bombard it with protons, you end up with an 18-fluorene molecule where an oxygen used to be. The compound, known as 2-fluoro-2-deoxydeglucose, will be referred to simply as FDG for the purposes of this talk.

What happens when the FDG gets into the cell? Normally, glucose goes into the cell, undergoes glycolysis, followed by the Krebs cycle. Hexokinase phosphorilates the glucose, and then phosphohexose isomerase converts this glucose into the fructose form, which can then be used to generate energy. However, what happens with FDG? FDG is indeed phosphorilated, but the phosphorilated form is not a suitable substrate for phosphohexose isomerase. So it accumulates, to a large degree, in malignant cells. Then it radiates, and we are able to see it.

FDG is, indeed, the most common substrate used in PET scan. If we are going to be using it to evaluate head and neck oncology, it is important to know what areas of the head and neck uptake FDG normally in order to avoid generating false positives and negatives. The areas of the highest uptake are the soft palate and the palatine tonsils, and this is where a lot of false negatives. A radiologist might have difficulty interpreting a high tracer intensity in the tonsils as either normal tonsillar tissue or malignant transformation. Conversely, you can get a lot of false positives in the tongue or thyroid gland where you have very low amounts of tracer uptake. The area of real difficulty is the salivary glands, which have a very intermittent and fluid amount of tracer uptake. This can confuse the interpretation of FDG scans in salivary glands.

PET scanning has a very important role in the initial evaluation of squamous cell carcinoma of the oral cavity, oropharynx, and hypopharynx. It is that it is very useful for outcomes prediction. You can use it to counsel your patients about their prognosis. In a 2004 study done by Dr. Schwartz and colleagues of about 60 patients, they found that high FDG uptake is associated with a very poor prognosis. The top line with the dark black dots shows patients who have a very low FDG uptake. The bottom line with the clear dots shows patients with a high FDG uptake, and shows their disease-free survival time. What you see is that there is a significant increase in disease-free survival time in patients who have tumors that do not take up a lot of FDG at the primary tumor site.

PET scanning can also be very useful for cervical lymph node staging in squamous cell carcinoma. It has a highly increased sensitivity and specificity versus CT and MRI. This was first realized by Dr. Adams and colleagues in a study published in 1998, that showed that PET scanning had sensitivities and specificities approaching 95 percent in cervical lymph node staging, which is better than either CT or MRI for initial evaluation. This work has been confirmed by three subsequent studies done through 2003. The only area where it may be hazy is in the clinically N0 neck. We do a physical exam on a patient, we do a CT scan, and there is an N0 neck. That can alter the sensitivity of a PET scan. The specificity is not altered very much, but it can decrease the sensitivity of the PET scan and make it a little more equivocal.

PET scanning is also extremely valuable for the surveillance of these patients since it has extremely high negative predictive value and sensitivity for both head and neck persistence or recurrence or distant metastases. When screening these patients postoperatively or post-radiation, you can see if you got it all, if the tumor came back and whether there is metastasis. It is also extremely helpful as a screening tool—high negative predictive value for telling if the patient has a cancer or not.

Unfortunately, PET scanning does not have a very high positive predictive value, which diminishes the value of a positive PET scan. But a negative PET scan in the setting of a squamous cell carcinoma is very reliable. The only caveat is that you need to wait at least one month, if not more, after the patient has completed radiotherapy. One of the confounding factors of PET scanning is that if you are using FDG, you are looking for cells with a high metabolic rate. Tumor cells and inflammatory cells will also have this high metabolic rate. Radiation induces tissue inflammation, which can create a false positive result, so a wait of 4-6 weeks after completion of radiation is necessary.

To summarize what we are saying about squamous cell carcinoma, PET scanning is a helpful initial diagnostic tool. It is very reliable for prognosis and cervical node staging. It is also excellent for post-treatment surveillance. A negative PET is very reliable in detecting any persistence or recurrence, as long as it is performed at least one month, if not more, after completion of radiotherapy.

PET scanning is also very useful in thyroid cancer. Highly differentiated tumors take up a lot of iodine. They do not going take up much FDG. Less differentiated tumors take up more FDG and less iodine. So, increased FDG uptake is associated with a poorer prognosis. Less differentiation, poor prognosis, increased FDG uptake. This can also be used to decide on the type of treatment or to counsel your patient. FDG-added tumors, being more poorly differentiated, have decreased iodine sensitivity, and a radioactive iodine will not work as well on these patients. A study was done in 2001 investigating 25 such patients who had FDG added and negative whole body scans. The study shows that tumors that were FDG added did not respond very well to radioactive iodine therapy. PET scanning is also very useful for the surveillance of thyroid cancer. It is an important addition to iodine whole body scans and thyroglobulin levels. A meta-analysis published in 2001 by McDougall and colleagues showed that when you have tumors that do not take up iodine on its own, they will take up FDG. The two work hand in hand in looking for tumor persistence or recurrence for distant metastases of thyroid cancer. In addition it is important to understand that FDG PET also has a much higher sensitivity and specificity than thyroglobulin levels. Thyroglobulin levels are normally used to try to detect those tumors that are missed by iodine whole body scans. FDG PET is important and better than that. Dr. Grunewald published a study of 222 patients evaluating the use of 131I whole body scans, FDG PET, and the two of them combined. He found that the two of them combined works best. This, I thought, was an interesting image to illustrate this point. This is a patient who has a vast amount of metastatic papillary thyroid cancer. The image on the left shows the patient’s iodine body scan. The image on the right is their PET scan. You can really see how the two work together to give you a true indication of what is going on with the patient.

PET is not very useful in medullary thyroid carcinoma. The existing literature shows that it is either equivocal to or inferior to CT or MRI in medullary thyroid cancer. Its main use refers to papillary and follicular thyroid carcinoma lesions.

To summarize PET’s role in thyroid cancer: helpful in prognosis, treatment, and surveillance. It is most useful for iodine-negative tumors, least accurate for well-differentiated tumors, and while there is little data available, it appears less useful than CT and MRI for medullary thyroid carcinoma.

The last tumor we are going to talk about in detail is laryngeal carcinoma. There is a great deal of interest now in using tyrosine-based PET scanning to image protein synthesis instead of metabolic rate for laryngeal cancer. You take a tyrosine atom, or tyrosine molecule, and turn one of the carbons into a radioactive carbon. Salts take it up and use it to synthesize protein, and it is very useful in imaging the protein synthesis rate. There has been some work done that indicates that protein synthesis rate can be an independent predictor of survival outcome in early tumors for laryngeal cancer. So, a tyrosine-based PET can help you counsel patients with laryngeal tumors about their five-year survival rates. Low-protein synthesis rate: high five-year-survival; higher protein synthesis rate: lower five-year survival. It is also very useful in surveillance. FDG PET is more sensitive and more specific than CT scan. A tyrosine PET is even better than FDG-based PET for the surveillance of laryngeal carcinoma.

This is an algorithm based on a study that has been proposed by researchers in The Netherlands. It is not necessarily accepted here in The United States yet, but it is an interesting concept—that much like squamous cell carcinoma, if the patient has a negative PET scan at your surveillance, your six-month or 12-month routine check-up for these patients, you can say there is no evidence of disease. If they have a positive PET scan, you want to proceed with further work-up. This can be fairly cost effective in evaluation of laryngeal cancer.

To summarize what we said for laryngeal cancer, tyrosine PET is useful for prognosis in that a high tracer uptake of tyrosine is associated with a poor prognosis. Tyrosine and FDG can both be used for cancer surveillance. Much like squamous cell carcinoma of the oral cavity and oropharynx, a negative PET is reliable and may very well be able to stand alone. A positive PET is not as reliable and warrants further investigation.

Lastly, I want to talk about a couple of less common cancers. First, carcinoma of unknown primary. PET has a very high sensitivity, specificity and accuracy. It is very useful for carcinoma of unknown primary. Sensitivities and specificities of protein are 90 percent—very useful. The important thing to keep in mind is that this is going to vary by location. If you get a positive tracer uptake in evaluation of a carcinoma of unknown primary in the tonsils, then you need to take this with a grain of salt, because, as you remember, the tonsils have a very high uptake of tracer under normal conditions, and it could very well be a false positive. But, usually with tumors in the base of tongue and other areas like that, it can be extremely useful. You will find about 25 percent additional primary tumors, about that many additional metastases, and it will end up changing your management in about a quarter of the cases of carcinoma of unknown primary.

With regards to nasopharyngeal carcinoma, it is a very useful complement to MRI. It doesn’t replace it, but it is very useful when used in conjunction with MRI.

The following are salivary gland neoplasms. Salivary glands have got variable fluid uptake on FDG tracer uptake, and so it is not very useful. In fact, benign tumors, such as a papillary cyst adenoma or lymphomatosis can look nearly identical to an adenoid cystic carcinoma on a PET scan, so a PET scan isn’t as useful for salivary gland neoplasms as it is for other tumors.

Finally, I want to talk about PET CT scanning. This is a new technique. Remember, PET provides low anatomic resolution. CT cannot image physiology but it has great anatomic resolution. If you combine the two—and this is an image from our patient—you end up with a PET CT, on the far right, compared to the CT on the left. On the PET scan, you see something lighting up, and PET CT can give you a precise anatomic location, down to about a 2 mm to 3 mm resolution level, precisely where the tracer is being taken up. It can be very useful. It can be superior to either modality. When used alone, it has very high sensitivity and specificity for nodal staging of squamous cell carcinomas. It is very useful for localizing recurrence of papillary thyroid carcinomas, and it may improve the accuracy of needle-guided CT biopsies.

So some of the key take-home points we have talked about. It is important to remember that PET scans are imaging physiology. We are looking at how cells work and not how tissue is structured. A high uptake is generally associated with a poorer prognosis. The higher uptake is going to indicate more avidly replicating cells and probably a more aggressive tumor.

It is highly accurate for initial staging of squamous cell carcinoma. Negative PET is very reliable for the surveillance of squamous cell carcinoma. With regards to the thyroid carcinoma, it is important to remember that it is an important addition to iodine whole body scans and thyroglobulin levels. It doesn’t replace them. It is an especially useful addition for iodine-negative tumors. It is not useful for medullary thyroid carcinoma. With regards to laryngeal squamous cell carcinoma, tyrosine PET can help in counseling your patients as it is important for prognosis. Both tyrosine and FDG PET are very useful for surveillance. Finally, PET CT scans have the potential to be superior to either scan alone, and there is a lot of research currently investigating its use in these tumors.

Case Presentation:

E.B. is a 67 year-old Caucasian woman who presented to an oral surgeon for management of a 1-2cm lesion on her hard palate. She was diagnosed with torus palatini and treated conservatively for several years. Initially, the lesion was not painful, and it neither grew nor caused any difficulty with eating, drinking, or swallowing. She had no significant tobacco or alcohol use history. However, the lesion eventually developed a painful, ulcerated center that caused discomfort with eating and swallowing. In July 2004, the lesion was excised by the patient’s oral surgeon and felt at that time to be benign. Unfortunately, the ulcer and discomfort persisted, and in December 2004, a biopsy was taken of the ulcer that revealed well-differentiated squamous cell carcinoma. The patient was referred to BCM Otolaryngology for further management.

Upon initial evaluation by our service, the patient was found to have a 2 cm non-healing, painful oral ulcer and a palpable level II left cervical lymph node. There were no other abnormalities on head and neck exam. PET/CT was performed and revealed intense tracer uptake in a left upper jugular lymph node. Based on these results, the patient underwent a partial palatectomy and left supraomohyoid neck dissection on February 18, 2005. Histological evaluation revealed well-differentiated squamous cell carcinoma with bony invasion and metastatic disease in three of eleven left sided cervical lymph nodes.

The patient recovered well from the operation and is now in week five of six of radiotherapy.

Bibliography:

Alnafisi NS , Driedger AA, Coates G, Moote DJ, Raphael SJ. FDG PET of recurrent or metastatic 131I-negative papillary thyroid carcinoma. J Nucl Med 2000;41:1010-1015.

Al-Nahhas A. Dedifferentiated thyroid carcinoma: The imaging role of 18F-FDG PET and non-iodine radiopharmaceuticals. Nucl Med Commun 2004;25:891-895.

Alavi A, Lakhani P, Mavi A, Kung JW, Zhuang H. PET: A revolution in medical imaging. Radiol Clin North Am 2004;42:983-1001.

Arvil N. GLUT1 expression in tissue and 18F-FDG uptake. J Nucl Med 2004;45:930-932.

Austin JR, Wong FC, Kim EE. Positron emission tomography in the detection of residual laryngeal carcinoma. Otoalryngol Head Neck Surg 1995;113:404-407.

Belhocine T, Pierard G, De Labrassinne M, Lahaye T, Rigo P. Staging of regional nodes in AJCC state I and II melanoma: 18FDG PET imaging versus sentinel node detection. Ongologist 2002;7:271-278.

Betka J. Distant metastases from lip and oral cavity cancer. ORL J Otorhinolaryngol Relat Spec 2001;63:217-221.

Beyer T, Townsend DW, Brun T, Kinahan PE, Charron M, Roddy R, Jerin J, Young J, Byars L, Nutt R. A combined PET/CT scanner for clinical oncology. J Nucl Med 2000;41:1369-1379.

Bockisch A, Beyer T, Antoch G, Freudenberg LS, Kuhl H, Debatin JF, Muller SP. Positron emission tomography/computed tomography-imaging protocols, artifacts and pitfalls. Mol Imaging Biol 2004;5:188-199.

Bongers V, Hobbelink MG, van Rijk PP, Hordijk GJ. Cost-effectiveness of dual-head 18F-fluorodeoxyglucose PET for the detection of recurrent laryngeal cancer. Cancer Biother Radiopharm 2002;17:303-306.

Brouwer J, Bodar EJ, De Bree R, Langendijk JA, Castelijns JA, Hoekstra OS, Leemans CR. Detecting recurrent laryngeal carcinoma after radiotherapy: Room for improvement. Eur Arch Otorhinolaryngol 2004;261:417-422.

Brouwer J, de Bree R, Comans EF, Castelijns JA, Hoekstra OS, Leemans CR. Positron emission tomography using [18F]fluorodeoxyglucose (FDG-PET) in the clinically negative neck: Is it likely to be superior? Eur Arch Otorhinolaryngol 2004;261:479-483.

Bui CD, Ching AS, Carlos RC, Shreve PD, Mukherji SK. Diagnostic accuracy of 2-[fluorine-18{fluoro-2-deoxy-D-glucose positron emission tomography imaging in nonsquamous tumors of the head and neck. Invest Radiol 2003;38:598-601.

Buss S, Grau C, Munk OL, Bender D, Jensen K, Keiding S. 11C-methionine PET, a noval method for measuring regional salivary gland function after radiotherapy of head and neck cancer. Radiother Oncol 2004;73:289-296.

Chan SC , Ng SH, Tzu-Chen Y, Chang JT, Chen TM. False-positive findings on F-18 fluoro-2-deoxy-D-glucose positron emission tomography in a patient with nasopharyngeal carcinoma and extensive sinusitis. Clin Nucl Med 2005;30:62-63.

Chander S, Webster GC, Zingas AP, Zak IT, Joyrich RN, Zerin JM, Bloom DA, Littrup PJ. American Burkitt’s lymphoma of the head and neck: Evaluation with serial FGD-PET. Clin Nucl Med 2004;29:646-648.

Chander S, Zingas AP, Bloom DA, Zak IT, Joyrich RN, Getzen TM. Positron emission tomography in primary thyroid lymphoma. Clin Nucl Med 2004;29:572-573.

Choi JY, Jang HJ, Shim YM, Kim K, Lee KS, Lee KH, Choi Y, Choe YS, Kim BT. 18F-FDG PET in patients with esophageal squamous cell carcinoma undergoing curative surgery: Prognostic implications. J Nucl Med 2004;45:1843-1850.

Chung JK So Y, Lee JS, Choi CW, Lim SM, Lee DS, Hong SW, Youn YK, Lee MC, Cho BY. Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan. J Nucl Med 1999; 40:986-992.

Civantos FJ, Gomez C, Duque C, Pedroso F, Goodwin WJ, Weed DT, Arnold D, Moffat F. Sentinel node biopsy in oral cavity cancer: Correlation with PET scan and immunohistochemistry. Head Neck 2003;25:1-9.

Cohen MS, Arslan N, Dehdashti F, Doherty GM, Lairmore TC, Brunt LM, Moley JF. Risk of malignancy in thyroid incidentalomas identified by fluorodeoxyglucose-positron emission tomography. Surgery 2001;130:941-946.

Davis PW, Perrier ND, Adler L, Levine EA. Incidental thyroid carcinoma identified by positron emission tomography scanning obtained for metastatic evaluation. Am Surg 2001;67:582-584.

Davis E, Solis V, Rosenberg RJ, Spencer RP. Asymmetric tongue muscle uptake of F-18 FDG: possible marker for cranial nerve XII paralysis. Clin Nucl Med 2004;29:531-533.

de Boer JR, Pruim J, Albers FW, Burlage F, Vaalburg W, van der Laan BF. Prediction of survival and therapy outcome with 11C-tyrosine PET in patients with laryngeal carcinoma. J Nucl Med 2004;45:2052-2057.

de Boer JR, Prium J, Burlage F, Krikke A, Tiebosch AT, Albers FW, Vaalburg W, Van Der Laan BF. Therapy evaluation of laryngeal carcinomas by tyrosine-pet. Head Neck 2003;25:634-644.

Dietlein M, Scheidhauer K, Voth E, Theissen P, Schicha H. Fluorine-18 fluorodeoxyglucose positron emission tomography and iodine-131 whole-body scintigraphy in the follow-up of differentiated thyroid cancer. Eur J Nucl Med 1997;24:1342-1348.

Farber LA, Benard F, Machtay M, Smith RJ, Weber RS, Weinstein GS, Chalian AA, Alavi A, Rosenthal DI. Detection of recurrent head and neck squamous cell carcinomas after radiation therapy with 2-18F-fluoro-2-deoxy-D-glucose positron emission tomography. Laryngoscope 1999;109:970-975.

Feine U. Fluor-18-deoxyglucose positron emission tomography in differentiated thyroid cancer. Eur J Endocrinol 1908;138:492-496.

Fox JL. PET scan controversy aired. Science 1984;324:143-144.

Friedman KP, Wahl RL. Clinical use of positron emission tomography in the management of cutaneous melanoma. Semin Nucl Med 2004;34:242-253.

Freudenberg LS, Antoch G, Jentzen W, Pink R, Knust J, Gorges R, Muller SP, Bockisch A, Debatin JF, Brandau W. Value of (124)I-PET/CT in staging of patients with differentiated thyroid cancer. Eur Radiol 2004;14:2092-2098.

Goerres GW, Haenggeli CA, Allaoua M, Albrecht SR, Dulguerov P, Becker M, Allal AS, Lehmann W, Slosman DO. Nuklearmedizin 2000;39:246-250.

Gotthardt M, Battmann A, Hoffken H, Schurrat T, Pollum H, Beuter D, Gratz S, Behe M, Bauhofer A, Klose KJ, Behr TM. 18F-FDG PET, somatostatin receptor scintigraphy, and CT in metastatic medullary thyroid carcinoma: A clinical study and an analysis of the literature. Nuc Med Commun 2004;25:439-443.

Grunwald F, Kalicke T, Feine U, Lietzenmayer R, Scheidhauer K, Dietlein M, Schober O, Lerch H, Brandt-Mainz K, Burchert W, Hiltermann G, Cremerius U, Biersack HJ. Fluorine-18 fluorodeoxyglucose positron emission tomography in thyroid cancer: Results of a multicentre study. Eur J Nucl Med 1999;26:1547-1552.

Hain SF. Positron emission tomography in cancer of the head and neck. Br J Oral Maxillofac Surg 2005;43:1-6.

Hollenbeck CS, Lowe VJ, Stack BC Jr. The cost-effectiveness of fluorodeoxyglucose 18-F positron emission tomography in the N0 neck. Cancer 2001;92:2341-2348.

Hooft L, Hoekstra OS, Deville W, Lips P, Teule GJ, Boers M, van Tulder MW. Diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography in the follow-up of papillary or follicular thyroid cancer. J Clin Endocrinol Metal 2001;86:3779-3786.

Hybrid PET-CT simulation for radiation treatment planning in head and neck cancers: A brief technical report. Int J Radiat Oncol Biol Phys 2004;60:1419-1424.

Hyde NC, Prvulovich E, Newman L, Waddington WA, Visvikis D, Ell P. A new approach to pre-treatment assessment of the N0 neck in oral squamous cell carcinoma: The role of sentinel node biopsy and positron emission tomography. Oral Oncol 2003;39:350-360.

Iwata M, Kasagi K, Misaki T, Matsumoto K, Iida Y, Ishimori T, Nakamoto Y, Higashi T, Saga T, Konishi J. Comparison of whole-body 18F-FDG PET, 99mTc-MIBI SPET, and post-therapeutic 1311-Na scintigraphy in the detection of metastatic thyroid cancer. Eur J Nucl Med Mol Imaging 2004;31:491-498.

Jadvar H, McDougall IR, Segall GM. Evaluation of suspected recurrent papillary thyroid carcinoma with [18F]fluorodeoxyglucose positron emission tomography. Nucl Med Commun 1998;19:547-554.

Jerusalem G, Hustinx R, Beguin Y, Fillet G. PET scan imaging in oncology. Eur J Cancer 2003;39:1525-1534.

Johansen J, Eigtved A, Buchwald C, Theilgaard SA, Hansen HS. Implication of 18F-fluoro-2-deoxy-D-glucose positron emission tomography on management of carcinoma of unknown primary in the head and neck: A Danish cohort study. Laryngoscope 2002;112:2009-2014.

Kapoor V, Fukui MB, McCook BM. Role of 18FFDG PET/CT in the treatment of head and neck cancers: Posttherapy evaluation and pitfalls. AJR Am J Roentgenol 2005;184:589-597.

Kato H, Miyazaki T, Nakajima M, Takita J, Kimura H, Faried A, Sohda M, Fukai Y, Masuda N, Fukuchi M, Manda R, Ojima H, Tsukada K, Kuwano H, Oriuchi N, Endo K. The incremental effect of positron emission tomography on diagnostic accuracy in the initial staging of esophageal carcinoma. Cancer 2005;103:148-156.

Khan N, Oriuchi N, Ninomiya H, Higuchi T, Kamada H, Endo K. Positron emission tomographic imaging with 11C-choline in differential diagnosis of head and neck tumors: comparison with 18F-FDG PET. Ann Nucl Med 2004;18:409-417.

Kim HJ, Boyd J, Dunphy F, Lowe V. F-18 FDG PET scan after radiotherapy for early-stage larynx cancer. Clin Nucl Med 1998;23:750-752.

Klabbers BM de Munck JC, Slotman BJ, Langendijk HA, de Bree R, Hoekstra OS, Boellaard R, Lammertsma AA. Matching PET and CT scans of the head and neck area: Development of method and validation. Med Phys 2002;29:2230-2238.

Kneist W, Schreckenberger M, Bartenstein P, Menzel C, Oberholzer K, Junginger T. Prospective evaluation of positron emission tomography in the preoperative staging of esophageal carcinoma. Arch Surg 2004;139:1043-1049.

Kubota K, Yokoyama J, Yamaguchi K, Ono S, Qureshy A, Itoh M, Fukuda H. FDG-PET delayed imaging for the detection of head and neck cancer recurrence after radio-chemotherapy: Comparison with MRI/CT. Eur J Nucl Med Mol Imaging 2004;31:590-595.

Kumar R, Mavi A, Bural G, Alavi A. Fluorodeoxyglucose-PET in the management of malignant melanoma. Radiol Clin North Am 2005;43:23-33.

Kunkel M, Forster GJ, Reichert TE, Jeong JH, Benz P, Bartenstein P, Wagner W, Whiteside TL. Detection of recurrent oral squamous cell carcinoma by [18F]-2-fluorodeoxyglucose-positron emission tomography: Implications for prognosis and patient management. Cancer 2003;98:2257-2265.

Larson SM, Robbins R. Positron emission tomography in thyroid cancer management. Semin Roentgenol 2002;37:169-174.

Liu SH, Chang JT, Ng SH, Chan SC, Yen TC. False positive fluorine-18 fluorodeoxy-D-glucose positron emission tomography finding caused by osteoradionecrosis in a nasopharyngeal carcinoma patient. Br J Radiol 2004;77:257-260.

Lonneux M, Lawson G, Ide C, Bausart R, Remacle M, Pauwels S. Positron emission tomography with fluorodeoxyglucose for suspected head and neck tumor recurrence in the symptomatic patient. Laryngoscope 2000;110:1493-1497.

McDougall IR, Davidson J, Segall GM. Positron emission tomography of the thyroid, with an emphasis on thyroid cancer. Nucl Med Commun 2001;22:485-492.

Mackie GC, Yarram SG. Pleomorphic adenoma simulating metastatic squamous cell carcinoma on f-18 fluorodeoxyglucose positron emission tomography. Clin Nucl Med 2004;29:743-744.

Makitie AA, Reis PP, Irish J, Zhang T, Chin SF, Chen X, Marriott C, Keller A, Perez-Ordonez B, Kamel-Reid S, Siu LL. Correlation of Epstein-Barr virus DNA in cell-free plasma, functional imaging and clinical course in locally advanced nasopharyngeal cancer: A pilot study. Head Neck 2004;26:815-822.

Minn H, Paul R, Ahonen A. Evaluation of treatment response to radiotherapy in head and neck cancer with fluorine-18 fluorodeoxyglucose. J Nucl Med 1988;29:1521-1525.

Myers LL, Wax MK, Nabi H, Simpson GT, Lamonica D. Positron emission tomography in the evaluation of the N0 neck. Laryngoscope 1998;108:232-236.

Nahas Z, Goldenberg D, Fakhry C, Ewertz M, Zeiger M, Ladenson PW, Wahl R, Tufano RP. The role of positron emission tomography/computed tomography in the management of recurrent papillary thyroid carcinoma. Laryngoscope 2005;115:237-243.

Nakamoto Y, Tatsumi M, Hammound D, Cohade C, Osman MM, Wahl RL. Normal FDG distribution patterns in the head and neck: PET/CT evaluation. Radiology 2005;234:879-885.

Ng SH, Chang JT, Chan SC, Ko SF, Wang HM, Liao CT, Chang YC, Yen TC. Nodal metastases of nasopharyngeal carcinoma: Eur J Nucl Med Mol 2004;31:1073-1080.

Ng SH, Joseph CT, Chan SC, Ko SF, Wang HM, Liao CT, Chang YC, Lin WJ, Fu YK, Yen TC. Clinical usefulness of 18F-FDG PET in nasopharyngeal carcinoma patients with questionable MRI findings for recurrence. J Nucl Med 2004;45:1669-1676.

Poppe K, Lahoutte T, Everaert H, Bossuyt A, Velkeniers B. The utility of multimodality imaging in anaplastic thyroid carcinoma. Thyroid 2004;14:981-982.

Raichle ME, Ter-Pogossian MM. PET scan controversy. Science 1984;224:934.

Rogers JW, Greven KM, McGuirt WF, Keyes JW Jr, Williams DW 3 rd, Watson NE, Geisinger K, Cappellari JO. Can post-RT neck dissection be omitted for patients with head and neck cancer who have a negative PET scan after definitive radiation therapy? Int J Radiat Oncol Biol Phys 2004;58:306-307.

Rusthoven KE, Koshy M, Paulino AC. The role of fluorodeoxglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor. Cancer 2004;101:2641-2649.

Ryan WR, Fee WE Jr, Le QT, Pinto HA. Positron-emission tomography for surveillance of head and neck cancer. Laryngoscope 2005;115:645-650.

Seki K, Hashimoto K, Hisada T, Maeda M, Satoh T, Uehara Y, Matsumoto H, Oyama T, Yamada M, Mori M. A patient with classic severe primary hyperparathyroidism in whom both Tc-99m MIBI scintigraphy and FDG-PET failed to detect the parathyroid tumor. Intern Med 2004;43:816-823.

Sercarz JA, Bailet JW, Abemayor E, Anzai Y, Hoh CK, Lufkin RB. Computer coregistration of positron emission tomography and magnetic resonance images in head and neck cancer. Am J Otolaryngol 1998;19:130-135.

Sharma R, Mondal A, Shankar LR, Sahoo M, Bhatnagar P, Sawroop K, Chopra MK, Kashyap R. Differentiation of malignant and benign solitary thyroid nodules using 30- and 120-minute tc-99m MIBI scans. Clin Nucl Med 2004;29:534-537.

Sigg MB, Steinert H, Gratz K, Hugenin P, Stoeckli S, Eyrich GK. Staging of head and neck tumors: [18F]fluorodeoxyglucose positron emission tomography compared with physical examination and conventional imaging modalities. J Oral Maxillofac Surg 2003;61:1022-1029.

Schecter NR, Gillenwater AM, Byers RM, Garden AS, Morrison WH, Nguyen LN, Podoloff DA, Ang KK. Can positron emission tomography improve the quality of care for head and neck cancer patients? Int J Radiat Oncol Biol Phys 2001;5:4-9.

Schechter NR, Wendt RE 3 rd, Yang DJ, Azhdarinia A, Erwin WD, Stachowiak AM, Broemelling LD, Kim EE, Cox JD, Podoloff DA, Ang KK. Radiation dosimetry of 99mTc-labeled C225 in patients with squamous cell carcinoma of the head and neck. J Nucl Med 2004;45:1683-1687.

Schwartz DL, Ford E, Rajendran J, Yueh B, Coltrera MD, Virgin J, Anzai Y, Haynor D, Lewellyn B, Mattes D, Meyer J, Phillips M, Leblanc M, Kinahan P, Krohn K, Eary J, Laramore GE. FDG-PET/CT imaging for preradiotherapy staging of head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2005;61:129-136.

Schwartz DL, Rajendran J, Yueh B, Coltrera MD, Leblanc M, Eary J, Krohn K. FDG-PET prediction of head and neck squamous cell cancer outcomes. Arch Otolaryngol Head Neck Surg 2004;130:1361-1367.

Seemann MD. PET/CT: Fundamental principles. Eur J Med Res 2004;9:241-246.

Stoeckli SJ, Steinert H, Pfaltz M, Schmid S. Is there a role for positron emission tomography with 18F-fluorodeoxyglucose in the initial staging of nodal negative oral and oropharyngeal squamous cell carcinoma. Head Neck 2002;24:345-349.

Sturkenboom MG, Franssen EJ, Berkhof J, Hoekstra OS. Physiological uptake of [18F]fluorodeoxglucose in the neck and upper chest region: Are there predictive characteristics? Nucl Med Commun 2004;25:1109-1111.

Terhaard CH, Bongers V, van Rijk PP, Hordijk GJ. F-18-fluoro-deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/pharyngeal cancer. Head Neck 2001;23:933-941.

Tian M, Zhang H, Oriuchi N, Higuchi T, Endo K. Comparison of 11C-choline PET and FDG PET for the differential diagnosis of malignant tumors. Eur J Nucl Med Mol Imaging 2004;31:1064-1072.

Townsend D, Byars L, Defriset M, Geissbuhler A, Nutt R. Rotating positron tomographs revisited. Phys Med Biol 1994;39:401-410.

Uematsu H, Sadato N, Ohtsubo T, Tsuchida T, Nakamura S, Sugimoto K, Waki A, Takashi N, Yonekura Y, Tsuda G, Saito H, Hayashi N, Yamamoto K, Ishii Y. Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of thyroid tumors. J Nucl Med 1998;39:453-459.

Van den Bruel A, Maes A, De Potter T, Mortelmans L, Drijkoningen M, Van Damme B, Delaere P, Bouillon R. Clinical relevance of thyroid fluorodeoxyglucose-whole body positron emission tomography incidentaloma. J Clin Endocrinol Metal 2002;87:1517-1520.

von Schulthess GK. Positron emission tomography versus positron emission tomography/computed tomography: From “unclear” to “new-clear” medicine. Mol Imaging Biol 2004;6:183-187.

Vrieze O, Haustermans K, DeWever W, Lerut T, Van Cutsem E, Ectors N, Hiele M, Flamen P. Is there a role for FGD-PET in radiotherapy planning in esophageal carcinoma? Radiother Oncol 2004;73:269-275.

Walsh RM, Wong WL, Chevretton EB, Beaney RP. The use of PET-18FDG imaging in the clinical evaluation of head and neck lymphoma. Clin Oncol (R Coll Radiol) 1996;8:51-54.

Wang W, Larson SM, Tuttle RM, Kalaigian H, Kolbert K, Sonenberg M, Robbins RJ. Resistance of [18f]-fluorodeoxyglucose-avid metastatic thyroid cancer lesions to treatment with high-dose radioactive iodine. Thyroid 2001;11:1169-1175.

Wax MK, Myers LL, Gabalski EC, Husain S, Gona JM, Nabi H. Positron emission tomography in the evaluation of synchronous lung lesions in patients with untreated head and neck cancer. Arch Otolaryngol Head Neck Surg 2002;128:703-707.

Wax MK, Myers LL, Gona JM, Husain SS, Nabi HA. The role of positron emission tomography in the evaluation of the N-positive neck. Otolaryngol Head Neck Surg 2003;129:163-167.

Wong RJ, Lin DT, Schoder H, Patel SG, Gonen M, Wolden S, Pfister DG, Shah JP, Larson SM, Kraus DH. Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma. J Clin Oncol 2002;15:20:4199-4208.

Yamamoto YL, Thompson CJ, Meyer E, Little J, Feindel W. Krypton-77 positron emission tomography for measurement of regional cerebral blood flow in a cross section of the head. Acta Neurol Scand Suppl 1977;64:448-449.

Yao M, Buatti JM, Dornfeld KJ, Graham MM, Smith RB, Funk GF, Hoffman HT. Can post-RT FDG PET accurately predict the pathologic status in neck dissection after radiation for locally advanced head and neck cancer? Int J Radiat Oncol Biol Phys 2005;61:306-307.

Yao M, Graham MM, Hoffman HT, Smith RB, Funk GF, Graham SM, Dornfeld KJ, Skwarchuk M, Menda Y, Buatti JM. The role of post-radiation therapy FDG PET in prediction of necessity for post-radiation therapy neck dissection in locally advanced head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2004;59:1001-1010.

Yao M, Graham MM, Smith RB, Dornfeld KJ, Skwarchuk M, Hoffman HT, Funk GT, Graham SM, Menda Y, Buatti JM. Value of FDG PET in assessment of treatment response and surveillance in head and neck cancer patients after intensity modulated radiation treatment: A preliminary report. Int J Radiat Oncol Biol Phys 2004;60:1410-1418.

Zhuang H, Kumar R, Mandel S, Alavi a. Investigation of thyroid, head, and neck cancers with PET. Radiol Clin North Am 2004;42:1101-1111.

Grand Rounds Archive | Department Home page