Radiation safety considerations for the bone seeking radiopharmaceuticals. 89SrCl2, 186Re-HEDP and 153Sm-EDTMP.

UNLABELLED: The radiation exposure to bystanders from 89SrCl2, 186Re-HEDP and 153Sm-EDTMP, is generally thought to be caused by "bremsstrahlung" and gamma-radiation, with negligible contribution from beta-radiation. The latter assumption may be erroneous. The aim of this prospective study was the investigation of radiation safety after treatment with these radiopharmaceuticals. The radiation field around treated patients was characterized and the magnitude estimated. PATIENTS, METHODS: 33 patients (30 prostate carcinoma, 3 breast carcinoma) were treated with 150 MBq 89SrCl2 (9 patients), 1295 MBq 186Re-HEDP (12 patients) or 37 MBq/kg 153Sm-EDTMP (12 patients). External exposure rates at 30 cm from the patient were measured at times 0 to 72 h post-injection. To evaluate the respective contribution of Bremsstrahlung, beta- and gamma-radiation, a calibrated survey meter was used, equipped with a shutter. For each patient, the measured exposure rate-versus-time data were fit to a curve and the curve integrated (area under the curve) to estimate the total exposure. RESULTS: For 29/33 patients the total ambient equivalent doses (mean+/-1 standard deviation [SD]) based on the integral of the fitted curve were 2.1+/-1.2 mSv for 89SrCl2, 3.3+/-0.6 mSv for 186Re-HEDP and 2.8+/-0.6 mSv for 153Sm-EDTMP. Beta-radiation contributes significantly to these doses (>99% for 89SrCl2, 87% for 186Re-HEDP and 27% for 153Sm-EDTMP). The effective doses (at 30 cm) are <0.1 mSv for 89SrCl2, 0.3 mSv for 186Re-HEDP and 1.6 mSv for 153Sm-EDTMP. CONCLUSION: Patients treated with 89SrCl2, 186Re-HEDP or 153Sm-EDTMP emit a spectrum of radiation, including non-negligible beta-radiation. With specific instructions effective doses to bystanders are acceptable.

Bone seeking radiopharmaceuticals for palliation of pain in cancer patients with osseous metastases.

Many patients with cancer develop symptomatic skeletal metastases at an advanced stage of their disease. Skeletal metastases are often complicated by pain. They cause considerable morbidity and mortality. Besides analgesics, treatment options include external beam radiotherapy, bisphosphonates, chemotherapy, surgery and bone seeking radiopharmaceuticals. Pain palliation with bone seeking radiopharmaceuticals has proved to be an effective treatment modality in patients with metastatic bone pain. Radiopharmaceuticals bind to the bone matrix in areas of increased bone turnover, due to a metastatic response. Beta rays from the specific radionuclide, bound to its carrier ligand, result in the therapeutic effect. Various radiopharmaceuticals have been developed for this purpose. All have their own characteristics. The radiopharmaceuticals Samarium-153-ethylenediaminetetramethylenephosphonic acid ((153)Sm-EDTMP) and Strontium-89-Chloride, which are approved in the USA and Europe, as well as the not universally approved Rhenium-186-hydroxyethylidenediphosphonic acid ((186)Re-HEDP), will be discussed in greater detail. Depending on the half-life and radiation energy of the specific radionuclide, they exert a different effect and toxicity profile. In most cases, bone marrow toxicity is limited and reversible, which makes repetitive treatment relatively safe. Several studies have shown encouraging clinical results of palliative therapy using bone seeking radiopharmaceuticals, with an overall reported pain response rate in the order of +/- 70-80% of patients. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. Additionally, new therapeutic strategies hold the promise of enhancement of the palliative and anticancer effects of this form of therapy.

Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application.

Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising systems for the treatment of liver malignancies. The microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method. After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. In this paper, the aspects of the production of a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10 patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS production process (sieving procedure, temperature control during evaporation and raw materials) were considered and the pharmaceutical quality of the microspheres was evaluated. The pharmaceutical characteristics (residual solvents, possible bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were in compliance with the requirements of the European Pharmacopoeia. Moreover, neutron irradiated Ho-PLLA-MS retained their morphological integrity and the holmium remained stably associated with the microspheres; it was observed that after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS which are produced as described in this paper, can be clinically applied, with respect to their pharmaceutical quality.

Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer.

The rapid developments of high-resolution imaging techniques are offering unique possibilities for the guidance and follow up of recently developed sophisticated anticancer therapies. Advanced biodegradable drug delivery systems, e.g. based on liposomes and polymeric nanoparticles or microparticles, are very effective tools to carry these anticancer agents to their site of action. Elements from the group of lanthanides have very interesting physical characteristics for imaging applications and are the ideal candidates to be co-loaded either in their non-radioactive or radioactive form into these advanced drug delivery systems because of the following reasons: Firstly, they can be used both as magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents and for single photon emission computed tomography (SPECT). Secondly, they can be used for radionuclide therapies which, importantly, can be monitored with SPECT, CT, and MRI. Thirdly, they have a relatively low toxicity, especially when they are complexed to ligands. This review gives a survey of the currently developed lanthanide-loaded microparticulate systems that are under investigation for cancer imaging and/or cancer therapy.

Simultaneous (99m)Tc/(201)Tl dual-isotope SPET with Monte Carlo-based down-scatter correction.

In simultaneous technetium-99m/thallium-201 dual-isotope (DI) single-photon emission tomography (SPET), down-scatter of (99m)Tc photons contaminates the (201)Tl image, which leads to a decrease in lesion contrast and loss of quantitative accuracy. Correction for down-scatter can be achieved by first reconstructing the (99m)Tc activity distribution. Subsequently, the (99m)Tc down-scatter in the (201)Tl photopeak window is simulated and used for correction during iterative reconstruction of the (201)Tl image. In this work, the down-scatter projections are calculated using a dedicated Monte Carlo simulator which is able to efficiently model the detection of lead X-rays from the collimator. An anthropomorphic torso phantom with a cardiac insert with and without cold lesions was used for evaluation of the proposed method. Excellent agreement in lesion contrast and quantitative accuracy was found between the down-scatter corrected DI-SPET (201)Tl image and the virgin (i.e. separately acquired) (201)Tl image, in particular when the effects of lead X-rays were included. Compensation for the noise added by down-scatter to the (201)Tl image can be achieved by using a 15% lower dose of (99m)Tc, a 15% increase in scan time and a 12% increase in (201)Tl dose. In conclusion, the Monte Carlo-based down-scatter correction recovers lesion contrast and quantitative accuracy in DI-SPET (201)Tl images almost perfectly. In addition, degradations due to the added noise of down-scatter in simultaneous DI-SPET can be prevented by slight adaptations to the data acquisition protocol.

Influence of neutron irradiation on holmium acetylacetonate loaded poly(L-lactic acid) microspheres.

Holmium-loaded microspheres are useful systems in radio-embolization therapy of liver metastases. For administration to a patient, the holmium-loaded microspheres have to be irradiated in a nuclear reactor to become radioactive. In this paper. the influence of neutron irradiation on poly(L-lactic acid) (PLLA) microspheres and films, with or without holmium acetylacetonate (HoAcAc), is investigated, in particular using differential scanning calorimetry (MDSC), scanning electron microscopy, gel permeation chromatography (GPC), infrared spectroscopy, and X-ray diffraction. After irradiation of the microspheres, only minor surface changes were seen using scanning electron microscopy, and the holmium complex remained immobilized in the polymer matrix as reflected by a relatively small release of this complex. GPC and MDSC measurements showed a decrease in molecular weight and crystallinity of the PLLA, respectively, which can be ascribed to radiation induced chain scission. Irradiation of the HoAcAc loaded PLLA matrices resulted in evaporation of the non-coordinated and one coordinated water molecule of the HoAcAc complex, as evidenced by MDSC and X-ray diffraction analysis. Infrared spectroscopy indicated that some degradation of the acetylacetonate anion occurred after irradiation. Although some radiation induced damage of both the PLLA matrix and the embedded HoAcAc-complex occurs, the microspheres retain their favourable properties (no marginal release of Ho, preservation of the microsphere size), which make these systems interesting candidates for the treatment of tumours by radio-embolization.

Advances in nuclear oncology: microspheres for internal radionuclide therapy of liver tumours.

Liver metastases cause the majority of deaths from colorectal cancer, and response to chemotherapy and external radiotherapy is poor. An alternative is internal radionuclide therapy using (90)Y labeled microspheres. These microspheres are very stable and have a proven efficacy in the field of treatment of primary or metastatic hepatic cancer. Whilst these glass spheres showed encouraging results in patients, their high density is a serious drawback. Currently, other materials with lower densities and other radioisotopes are being investigated in order to optimize this promising new therapy. Three major radiolabeled microsphere materials, viz. glass, resin-based and polymer-based, are now available for therapy or are being tested in animals. In this review the preparation, stability and degradation of these spheres are discussed.

Quantitative baseline renography 48 hours after renal transplantation predicts long-term graft survival.

Technetium-99m mercaptoacetylglycine (99mTc-MAG3) renography is a successful non-invasive method for the evaluation of renal transplants. In this study we prospectively studied 256 patients after renal transplantation, using the MAG3 uptake capacity in the first 10 min (MUC10), which is an index of renal function representing kidney activity as a fraction of the injected dose. Renal scintigraphy was performed in all patients within 48 h of transplantation. Renograms were obtained over 20 min, after bolus injection of +/-100 MBq 99mTc-MAG3. MUC10 ranged between 0.0 and 94.9. The patients were divided into five groups: group 1, MUC10 <1; group 2, 1< or =MUC10 < 5; group 3, 5 < or = MUC10 <10; group 4, 10 < or = MUC10 < 30; group 5, MUC10 > or =30. In 235 patients, follow-up for 5 years was completed. Considering all the renal transplants, 30% of the grafts ceased functioning within the first 5 years. Six grafts showed a MUC10 of < 1, and none survived the first year. After 5 years, 43% of the grafts with a MUC10 of 1-5 still functioned, as compared with 63% of those with a MUC10 of 5-10, 72% of those with a MUC10 of 10-30 and 83% of those with a MUC10 of > or =30. Kaplan-Meier survival analysis showed significant differences between the five different patient groups based on MUC10 in terms of the percentage of kidneys that ceased to function within 5 years. The period of cold ischaemia and the donor age were known in 178 patients. In contrast to cold ischaemia time, the MUC10 and the donor age showed a significant effect (P<0.05) on graft survival. This study indicates that the MUC10 early after renal transplantation is useful as a prognostic factor in the evaluation of kidney transplants and that a MUC10 of <1 indicates a dismal prognosis for the renal transplant.

Characterization of poly(L-lactic acid) microspheres loaded with holmium acetylacetonate.

Holmium-loaded PLLA microspheres are useful systems in radioembolization therapy of liver metastases because of their low density, biodegradability and favourable radiation characteristics. Neutron activated Ho-loaded microspheres showed a surprisingly low release of the relatively small holmium complex. In this paper factors responsible for this behaviour are investigated, in particular by the use of differential scanning calorimetry, scanning electron microscopy, infrared spectroscopy and X-ray diffraction. The holmium complex is soluble in PLLA up to 8% in films and 17% in microspheres. Interactions between carbonyl groups of PLLA, and the Ho-ion in the HoAcAc complex, explain very satisfactorily the high stability of holmium-loaded microspheres.

Impact of delayed gastric emptying on the outcome of antireflux surgery.

OBJECTIVE: To study the effect of Nissen fundoplication on the pattern of gastric emptying and intragastric distribution of symptoms in patients with normal and delayed gastric emptying before surgery, especially in those with delayed emptying before surgery. SUMMARY BACKGROUND DATA: Gastroesophageal reflux disease is associated with delayed gastric emptying and dyspeptic symptoms in approximately 40% of the patients. After Nissen fundoplication, dyspeptic symptoms are also not uncommon. METHODS: Thirty-six patients (26 men, 10 women, mean age 43.1) were studied before and 3 months after Nissen fundoplication. Gastric emptying (dual-isotope, expressed in lag phase, emptying rate, T50, and intragastric distribution) was not included in the decision for surgery. Reflux-related and dyspeptic symptoms were scored before and at 3, 6, and 12 months after surgery. RESULTS: Twenty-six patients had normal and 10 had delayed gastric emptying before surgery. Nissen fundoplication on average enhanced gastric emptying for solids in both subgroups by a combination of a decrease in mean lag phase, emptying rate, and T50. The preoperative difference in intragastric distribution between patients with and without delayed gastric emptying was abolished by fundoplication. Patients with normal gastric emptying before surgery showed an increase in early postprandial satiety; in those with delayed emptying, this was not observed. A correlation was found between preoperative T50 for liquid gastric emptying and postoperative nausea at 3 months in patients with normal gastric emptying. In patients with delayed emptying, preoperative correlations between lag phase for liquids and nausea respectively early satiety were significant, as well as for T50 for liquids and vomiting. CONCLUSIONS: Nissen fundoplication equalizes the preoperative difference in intragastric distribution and accelerates gastric emptying without an effect on symptoms in patients with preexisting delayed gastric emptying, but with an increase in early satiety in patients with normal gastric emptying. Delayed gastric emptying is not a contraindication for antireflux surgery.

Captopril renography and the relevance of abnormal but bilateral identical curves in the diagnosis of renal artery stenosis.

BACKGROUND: Captopril renography (CR) has been shown to improve the effectiveness of renal scintigraphy in renovascular hypertension, by inhibiting angiotensin-converting enzyme. CR is particularly sensitive and specific in unilateral renal artery stenosis (RAS), but results in patients with bilateral RAS are less favourable. The aim of this study was to investigate the meaning of abnormal but identical renographic curves in the diagnosis of RAS. PATIENTS AND METHODS: One hundred and fifty-eight patients clinically suspected for renovascular hypertension underwent CR, using 50 MBq (99)Tc(m)-mercaptoacetyltriglycine ((99)Tc(m)-MAG(3)), prior to performing renal angiography. CR was performed 1 h after captopril administration. Renograms were analysed according to the consensus criteria. All patients underwent angiography, considered as the "gold standard" in the detection of the presence of RAS (stenosis >50% was defined as significant). All kidneys were categorized into three groups, scintigraphically as well as angiographically: no stenosis, unilateral stenosis and bilateral stenosis. RESULTS: Out of 158 patients 100 (63%) showed a RAS on angiography (58 (37%) unilateral, 42 (26%) bilateral). The sensitivity and specificity of CR evaluated by patient was 83% and 75%, respectively. Thirty patients with completely identical curves were identified, 21 patients with normal curves and nine patients with abnormal identical curves. All but one patient showed no RAS on the angiogram. In this single patient a unilateral stenosis was found. CONCLUSION: Identical curves on the renogram generally suggest no RAS and are probably due to intrinsic parenchymal disease.

186Re-etidronate. Efficacy of palliative radionuclide therapy for painful bone metastases.

Pain palliation with bone-seeking radiopharmaceuticals is an effective treatment modality in patients with advanced metastatic bone cancer. Several studies have shown encouraging clinical results of palliative therapy using 186Re-HEDP, with an overall reported response rate of +/-71% for painful osseous metastasized prostate and breast cancer patients. 186Re-HEDP is a very potential isotope with numerous advantageous characteristics for this purpose. Myelosuppressive toxicity is limited and reversible, which makes repetitive treatment safe. However, individual studies are difficult to compare, and are hampered by the numerous and different methods used to assess clinical response. Standardized clinical response assessment using the objective multi-dimensional pain evaluation model should therefore be implemented.

Methotrexate osteopathy demonstrated by Technetium-99m HDP bone scintigraphy.

The authors report a case of methotrexate osteopathy as revealed by Tc-99m HDP bone scintigraphy in a patient with rheumatoid arthritis. Methotrexate is used widely in high doses as a chemotherapeutic agent. Lower doses are given in rheumatoid and psoriatric arthritis. Methotrexate affects bone metabolism, resulting in methotrexate osteopathy, characterized by osteoporosis, osseus pain, and even spontaneous (micro)fractures. Radiographic visualization of microfractures is difficult. Tc-99m HDP bone scans have been shown to be very sensitive in the visualization of changes in bone metabolism as a result of methotrexate osteopathy.

Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin.

Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 microg/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients.

European Medical Device Directive: impact on nuclear medicine.

The European Council Directive 93/42/EEC concerning medical devices (14 June 1993) assigns new responsibilities and imposes technical requirements both to the manufacturer and user of medical devices. In this paper the general outlines of the directive are discussed with a particular emphasis on the risk classification of products, the compliance and evaluation process and the CE-marking regulations. Furthermore, some practical implications are highlighted for devices and tools relevant to the field of nuclear medicine such as radiation detectors, gamma- and PET-cameras and software.

F-18-fluoro-deoxy-glucose positron-emission tomography scanning in detection of local recurrence after radiotherapy for laryngeal/ pharyngeal cancer.

BACKGROUND: The objective of this investigation was to determine whether F18-fluoro-deoxy-glucose (FDG) positron-emission tomography (PET) could differentiate between local recurrence and late radiation effects after radiotherapy for laryngeal/pharyngeal cancer. METHODS: In a prospective study of 75 patients (67 larynx, eight oro/hypopharynx), 160 laryngoscopies and 109 FDG PET scans were performed on the head and neck region. The mean follow-up time after the first FDG PET scan was 23 months (minimum 1 year). RESULTS: Local recurrence was diagnosed in 37 patients: 19 after the first biopsy and 18 after follow-up biopsies. For all of the negative initial FDG scans (27), the biopsies that were taken at the same time were negative and no recurrence was seen for at least 1 year. The first FDG scan was a true positive in 34 of 48 patients. In 12 of the 14 patients with false-positive results, FDG scans were repeated; a decreased FDG uptake was found in 9 of the 12. The sensitivity and specificity of the first scan were respectively 92% and 63%; including subsequent FDG scans, the rates were 97% and 82%, respectively. CONCLUSIONS: When a local recurrence is suspected after radiotherapy for cancer of the larynx/pharynx, an FDG PET scan should be the first diagnostic step. No biopsy is needed if the scan is negative. If the scan is positive and the biopsy negative, a decreased FDG uptake measured in a follow-up scan indicates that a local recurrence is unlikely.

Iodine-131 uptake and turnover rate vary over short intervals in Graves' disease.

From a Dutch questionnaire, it was apparent that nearly all institutions used percentage of radioiodine uptake for calculation of the radioiodine dose in Graves' disease. Although there is a general belief that fluctuations in radioiodine uptake may occur, with few exceptions relatively long intervals were accepted between the uptake measurement and the actual therapy dose. With the aim of optimizing the pretherapeutic work-up, we evaluated the stability of iodine uptake over time in patients with Graves' disease who were referred for 131I therapy. 131I uptake was measured in 300 consecutive patients for the calculation of the required 131I therapy dose; data were complete for 291 patients (97%). After discontinuing thyroid medication for 3 days, standardized thyroid probe measurements were performed 5 and 24 h after ingestion of a capsule containing 0.37 MBq 131I-NaI. Measurements were performed at the time of scintigraphic diagnosis (test 1), as well as immediately before 131I therapy (test 2). The time interval between test 1 and test 2 ranged from 2 to 421 (median 40) days. A relative increase or decrease greater than 10% between tests 1 and 2 occurred in 180 of 291 cases (62%) at 5 h and in 158 of 291 patients (54%) at 24 h. These changes were not related to the interval between the tests or to initial uptake values, thyroid mass, gender or age. Rapid turnover of radioiodine (5 h/24 h uptake ratio > 1) was noted in 17% of the patients during test 1 and in 15% during test 2. Rapid turnover was persistent (present in both tests 1 and 2) in only 9%. We conclude that patients with Graves' disease show considerable changes in 131I uptake over relatively short periods of time, and the turnover rate of 131I in this condition is not constant.

Minimizing liver, bowel, and gastric activity in myocardial perfusion SPECT.

UNLABELLED: When using 99mTc-tetrofosmin for myocardial perfusion SPECT, increased liver, intestinal, or gastric activity may create a major problem in the visual and quantitative interpretation Of the inferoposteroseptal walls, particularly at rest. The aim of this study was to determine what measures were required to minimize this extracardial activity. METHODS: Ninety-seven patients had a SPECT scan at rest without attenuation correction. They were divided into 3 groups. Preparation consisted of no action taken (group 1), 150 mL whole milk 10 min after administration of tetrofosmin (group 2), or 450 mL water 10 min before acquisition (group 3). A further 55 patients had a SPECT scan at rest with attenuation correction. They were also divided into 3 groups, and preparation consisted of 150 mL whole milk 10 min after administration of tetrofosmin (group 4), 450 mL water 10 min before acquisition (group 5), or both whole milk and water (group 6). The presence of activity in liver, bowel, and stomach was determined visually on reconstructed images. Activity was defined as interfering when it might result in either an underestimation or an overestimation of the uptake in the myocardial wall. RESULTS: Interfering activity was seen in 83% of the patients in group 1, in 74% in group 2, in 33% in group 3, in 61% in group 4, in 67% in group 5, and in 20% of group 6. CONCLUSION: The interpretation of inferoposteroseptal wall activity on myocardial rest SPECT images is facilitated by having the patient drink both whole milk and water at specified times before data acquisition.

Preoperative evaluation of patients with primary head and neck cancer using dual-head 18fluorodeoxyglucose positron emission tomography.

OBJECTIVE: To evaluate the value of 18fluorodeoxyglucose (FDG) positron emission tomography (PET) in primary head and neck cancer. BACKGROUND DATA: Head and neck carcinomas tend to metastasize to regional lymph nodes rather than to spread hematogenously. With nodal metastases, cure rates decrease by approximately 50%. Moreover, in approximately 3% of the patients, a second primary tumor is found at initial presentation. METHODS: Fifty-four consecutive patients (31 men and 23 women; mean age 60 years, range 34-81 years) with previously untreated squamous cell carcinomas of the oral cavity or oropharynx were studied. Before surgery and within a period of 3 weeks, clinical examination, chest x-ray, computed tomography (CT), ultrasonography with fine-needle aspiration cytology (US/ FNAC), and FDG-PET were performed. All study results were scored per neck side and were also classified as 0 (no metastases), 1 (single metastasis), or 2 (multiple metastases). RESULTS: The sensitivity for the detection of lymph node metastases per neck side was 96%, 85%, and 64% for FDG-PET, CT, and US/FNAC, respectively. The specificity was 90%, 86%, and 100% for FDG-PET, CT, and US/FNAC, respectively. In terms of the classification, FDG-PET showed the best correlation with the histologic data. Finally, in nine patients (17%), a second primary tumor was detected by FDG-PET and confirmed by histologic evaluation. CONCLUSION: Because of the high prevalence of second primary tumors detected by FDG-PET and the decreased error rate in the assessment of lymph node involvement compared with CT and US, FDG-PET should be routinely performed in patients with primary head and neck cancer.