Tau uptake in agrammatic primary progressive aphasia with and without apraxia of speech.

BACKGROUND AND PURPOSE: The non-fluent/agrammatic variant of primary progressive aphasia (agPPA) is a heterogeneous diagnosis wherein some individuals have apraxia of speech (AOS). When agPPA includes AOS, a tauopathy is the likely underlying pathology. Recently, [18F]AV-1451 was developed for the in-vivo assessment of tau. In this study, we compared patterns of tau tracer uptake in patients with agPPA with and without AOS. METHODS: Nine patients with agPPA (four without AOS) underwent tau positron emission tomography imaging with [18F]AV-1451. Uptake of [18F]AV-1451 was assessed as cortical to cerebellar crus ratio (standard uptake value ratio) in cortical regions of interest measured using the MCALT atlas and compared voxel-wise in SPM12. Each patient was age- and sex-matched to three controls. RESULTS: The agPPA without AOS showed uptake in the left frontal and temporal lobes, whereas agPPA with AOS showed uptake in the bilateral supplementary motor areas, frontal lobes, precuneus and precentral gyrus relative to controls. The left precentral gyrus had uptake in agPPA with AOS relative to those without AOS. CONCLUSIONS: This cross-sectional study suggests that [18F]AV-1451 uptake in the precentral gyrus is implicated in AOS in agPPA.

[18F] AV-1451 uptake in corticobasal syndrome: the influence of beta-amyloid and clinical presentation.

Corticobasal syndrome (CBS) is a phenotypic manifestation of diverse pathologies, including Alzheimer's disease and 4-repeat tauopathies. Predicting pathology in CBS is unreliable and, hence, molecular neuroimaging may prove to be useful. The aim of this study was to assess regional patterns of uptake on [18F] AV-1451 PET in CBS and determine whether patterns of uptake differ according to beta-amyloid deposition or differing clinical presentations. Fourteen patients meeting criteria for CBS underwent Pittsburgh Compound B (PiB) and [18F] AV-1451 PET. Seven patients presented as CBS and seven presented with apraxia of speech (AOS) and later evolved into CBS. A global PiB summary was calculated and used to classify patients as PiB (-) or PiB (+). AV-1451 uptake was calculated in fourteen regions-of-interest, with values divided by uptake in cerebellar crus grey matter to generate standard uptake value ratios. AV-1451 uptake was considered elevated if it fell above the 95th percentile from a group of 476 cognitively unimpaired normal controls. Six of the 14 CBS patients (43%) were PiB (+), with three of these patients showing strikingly elevated AV-1451 uptake across many cortical regions. Of the eight PiB (-) patients, only those with AOS showed elevated AV-1451 uptake in supplementary motor area and precentral cortex compared to controls. No region of elevated AV-1451 uptake were observed in PiB (-) typical CBS patients without AOS. These results suggest that regional [18F] AV-1451 is variable in CBS and depends on the presence of beta-amyloid as well as clinical presentation such as AOS. PiB (+) CBS does not necessarily reflect underlying Alzheimer's disease; however, the possibility some of these patients will evolve into Alzheimer's disease over time cannot be excluded.

Phase I trial of systemic administration of Edmonston strain of measles virus genetically engineered to express the sodium iodide symporter in patients with recurrent or refractory multiple myeloma.

MV-NIS is an Edmonston lineage oncolytic measles virus expressing the human sodium iodide symporter-a means for monitoring by non-invasive imaging of radioiodine. Patients with relapsed, refractory myeloma who had explored all other treatment options were eligible for this Phase I trial. Cohort 1 was treated with intravenous MV-NIS, and Cohort 2 received cyclophosphamide 2 days prior to MV-NIS. Thirty-two patients were treated. Cohort 1 initially enrolled to four dose levels without reaching maximum tolerated dose (MTD) and subsequently to two higher dose levels when improved virus manufacture technology made it possible. MTD was not reached in Cohort 1, and TCID50 1011 is the dose being used in a Phase II trial of single agent MV-NIS. Grade 3-4 adverse events in both cohorts at all dose levels were: neutropenia (n=9); leukocyte count decreased (n=5); thrombocytopenia (n=2); and CD4 lymphocytes decreased, anemia and lymphopenia (each n=1). MV-N RNA sequences were amplified from gargle specimens, blood and urine. 123I scans were positive in eight patients. One patient achieved a complete response; transient drops in serum free light chains were seen in other patients. MV-NIS is capable of replicating before being cleared by the immune system. Oncolytic viruses offer a promising new modality for the targeted infection and destruction of disseminated myeloma.

Regional ß-amyloid burden does not correlate with cognitive or language deficits in Alzheimer's disease presenting as aphasia.

BACKGROUND AND PURPOSE: A subset of patients with Alzheimer's disease (AD) present with early and prominent language impairment (aphasic AD). Our previous study demonstrated an association between global ß-amyloid burden measured on [(11)C] Pittsburgh compound B (PiB) positron emission tomography and general cognitive impairment, but not with aphasia, in such subjects. As a follow-up, whether there is any association between regional ß-amyloid burden, atrophy on magnetic resonance imaging (MRI) and global cognitive impairment, aphasia or other cognitive and functional impairment in aphasic AD is assessed. METHODS: Forty-four aphasic AD subjects who underwent PiB scanning and volumetric MRI and were determined to be positive for ß-amyloid deposition were analyzed. All had completed detailed neurological, neuropsychological and language batteries. Spearman's rank-order correlation was utilized to assess for associations. RESULTS: Greater visuospatial impairment was associated with increased ß-amyloid burden in the primary visual cortex (P = 0.001). Although there were many trends for associations between neurocognitive and language deficits and regional ß-amyloid burden, there were no strong associations that survived correction for multiple comparisons. However, neurocognitive and language impairment in these subjects strongly correlated with the degree of left lateral temporal and inferior parietal atrophy (P < 0.004). CONCLUSIONS: The findings from this study suggest a close relation between the severity of regional atrophy and cognitive and language impairment, but argue against a strong association between regional ß-amyloid burden and such deficits in aphasic AD subjects. Hence, other pathological factors may be driving the previously identified association between global ß-amyloid deposition and general cognitive impairment in aphasic AD.

Oncologic PET/CT interpretation and reporting approaches. Survey in clinical practice.

AIM: To elucidate techniques most commonly used for interpreting oncologic PET/CT studies. This survey forms a basis to work on standardization of reporting and highlight the most important issues to be addressed. METHODS: A web-based survey of 329 PET/CT imaging specialists was designed with the intent to determine image interpretation patterns. The questionnaire consisted of 19 questions. Of the 329 participants, 230 were nuclear medicine specialists, 46 were radiologists, and 53 had dual-board certification. RESULTS: Report ofstandardized uptake values (SUV) is not consistent;only50.2% of respondents always report SUVs, while 45.2% report only if needed or requested. 80.9% of respondents indicated that reporting of SUV is only appropriate when its limitations are understood whereby a large majority prefer to report SUVmax. Maximum intensity projection (MIP) images are almost always reviewed by 91.1% of the respondents. An accurate and detailed clinical history is considered an essential element for reading PET/CT studies by 84.0%, but only 20.7% report that this is always available. The most common self-reported average time for reviewing and reporting of whole body PET/CT (with no prior comparison scan) was 15-20 min (27.5%). CONCLUSION: PET readers have considerable reservations regarding the use and reporting of SUVs. SUVmax is more frequently used than SUVmean. Evaluation of MIP images is considered an important element of PET/CT interpretation. Although availability of sufficient patient's history is considered essential, this is rarely available.

Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin.

OBJECTIVE: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). METHODS: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. RESULTS: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. CONCLUSIONS: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease.

Effects of age on the glucose metabolic changes in mild cognitive impairment.

BACKGROUND AND PURPOSE: Decreased glucose metabolism in the temporal and parietal lobes on FDG-PET is recognized as an early imaging marker for the AD pathology. Our objective was to investigate the effects of age on FDG-PET findings in aMCI. MATERIALS AND METHODS: Twenty-five patients with aMCI at 55-86 years of age (median = 73 years) and 25 age- and sex-matched CN subjects underwent FDG-PET. SPM5 was used to compare the FDG uptake in patients in aMCI-old (>73 years) and aMCI-young (

Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan.

OBJECTIVES: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis. METHODS: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard. RESULTS: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis. CONCLUSION: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

Biodistribution and dosimetry of [(18)F]fluorodeoxyglucose labelled leukocytes in normal human subjects.

SUMMARY: This study was performed in order to assess [(18)F]fluorodeoxyglucose white blood cell ((18)F-FDG WBC) dosimetry in normal human subjects. Using previously reported methods, mixed cell suspensions of autologous leukocytes were prepared from four normal volunteers. Leukocytes were labelled in heparin-saline by incubation with (18)F-FDG at 37 degrees C for 20 min. After washing and resuspension, (18)F-FDG WBCs (225-315 MBq) were administered by intravenous injection. Whole-body imaging was performed at 0.5, 1, 2, 4 and 6 h using a GE Varicam with 511 keV collimation. Blood samples were obtained at corresponding times as well as fractionated urinary collection. Whole-body anterior and posterior images were used for calculation of organ dosimetry. Uptake of (18)F-FDG WBCs occurred predominantly within the reticulo-endothelial system. Plasma activity, urinary excretion (9.9+/-2.3% at 6 h), and brain uptake (1.7+/-0.4%) were consistent with partial elution of (18)F-FDG. Positron emission tomography imaging performed at 5-6 h after injection yielded good quality images of reticulo-endothelial uptake. Whole-body and organ dosimetry for (18)F-FDG WBCs in doses of 225-250 MBq are comparable with reported results for conventional doses of (111)In oxine labelled leukocytes. Further studies of (18)F-FDG WBC as an agent for positron emission tomography imaging of inflammatory disease appear warranted.

The cost-effectiveness of fluorodeoxyglucose 18-F positron emission tomography in the N0 neck.

BACKGROUND: Although surgery and radiation are effective treatments of regional lymphatics for classification N0 head and neck squamous cell carcinoma (HNSCC) patients, both have morbidities that could be avoided in approximately 70% of patients without lymph node disease with better diagnostic information. 18-F fluoro-2-deoxyglucose positron emission tomography (FDG-PET) has shown promise in detecting subclinical lymph node disease, but its cost and availability have limited its use. Here, we sought to determine whether the use of FDG-PET was cost-effective as part of a treatment strategy for classification N0 HNSCC patients. METHODS: The cost-effectiveness of proceeding from classification of N0 by computed tomography to a PET scan was estimated using standard methods of economic evaluation. Costs were for a large, Midwestern university medical center. Probabilities were computed from a review of the literature. Utilities were obtained by a time-tradeoff method, and life expectancy was estimated using the Surveillance, Epidemiology, and End Results database. Outcomes measures were cost per year of life saved and cost per quality-adjusted life-year. RESULTS: Modified radical neck dissection was associated with the lowest morbidity (utility [u] = 0.93), and radical neck dissection plus radiation was associated with the highest (u = 0.68). Life expectancy was estimated to be 5.9 and 11.5 years for patients with and without lymph node disease, respectively. The incremental cost-effectiveness ratio for the PET strategy was $8718 per year of life saved, or $2505 per quality-adjusted life-year. CONCLUSIONS: A diagnostic and treatment strategy that proceeds from classification of N0 to a PET scan is cost-effective. Prospective studies that evaluate this strategy are important to assure that these simulation results are realized in clinical practice.

The use of lymphoscintigraphy and PET in the management of head and neck melanoma.

OBJECTIVES: Lymphoscintigraphy with sentinel node dissection and 18 fluoro-2-deoxyglucose positron emission tomography (PET) are being used independently in the management of many intermediate and thick melanomas of the head and neck. We report a series of patients with melanoma of the head and neck with Breslow depths greater than 1.0 mm and clinically negative regional nodes that were evaluated prospectively with PET and lymphoscintigraphy. STUDY DESIGN AND SETTING: Between July 1, 1998 and December 30, 2000 PET scans were obtained preoperatively on 18 patients undergoing resection of head and neck melanoma. Lymphoscintigraphy and sentinel node dissection was performed. Resection of the primary lesion was then carried out with adequate margins and the defects were reconstructed. RESULTS: Sentinel node(s) were found in 17/18 patients (94.4%); 5/18 (27.8%) of cases had metastases. PET detected nodal metastasis preoperatively in 3 patients (16.7%), one of which had a positive sentinel node dissection. CONCLUSION: PET and lymphoscintigraphy offer complimentary ways of evaluation for metastatic melanoma.

18F-FDG labelling of human leukocytes.

Radiolabelled leukocytes are useful for the imaging of inflammation and infection, and 18F-fluorodeoxyglucose (18F-FDG) is known to concentrate in metabolically active cells. We evaluated the feasibility of leukocyte labelling with 18F-FDG using ACD and heparin anticoagulants at 20 degrees C and 37 degrees C, with and without gentle mixing during incubation. With leukocytes (WBC) harvested from 20 ml blood, studies were performed using 18F-FDG in concentrations of 3.7-74 MBq (0.1-2.0 mCi). 18F-FDG WBC stability in platelet-poor plasma was assessed at 1-4 h. Satisfactory labelling efficiency was achieved with incubation in heparin-saline at 37 degrees C for 30 min (62.7+/-1.6%), and was further enhanced by mixing during incubation (78.1+/-3.9%). Cell labelling was predominantly of granulocytes (78.5+/-1.4%). 18F-FDG WBC was relatively stable in platelet-poor plasma for up to 4 h, and no cell staining was observed in viability studies using trypan blue. These results indicate the feasibility of leukocyte labelling with 18F-FDG, providing an approach that may be useful in PET imaging of inflammation and infection.

Positron emission tomography scanning in the evaluation of hepatocellular carcinoma.

BACKGROUND/AIMS: 18F-fluorodeoxyglucose uptake allows estimation of glucose metabolism by tumor cells using positron emission tomography (PET). We evaluated the role of PET imaging in the diagnosis of hepatocellular carcinoma. METHODS: PET images were collected after intravenous injection of 8-12 mCi of 18F-FDG in 20 patients with hepatocellular carcinoma (HCC). PET tumor activity level was assessed on a scale of 1 to 4 compared to normal liver tissue. The PET score was compared with abdominal computerized tomography (CT) scan results and between tumors of different grades and differentiation. RESULTS: Of the 20 patients studied, 11 (55%) had positive PET scans (PET score: 3 or 4) while nine (45%) were negative (PET score: 1 or 2). CT scan was positive in 18 patients (90%) and negative in two (10%). PET, however, revealed metastases in three patients that were not seen on CT. On pathological review, well-differentiated and low-grade tumors had lower PET scores. Comparison of the well-differentiated with the moderately- and poorly-differentiated tumors revealed a statistically significant difference. No statistical significance was observed between the moderately- and poorly-differentiated tumors or between different tumor grades and PET scores. CONCLUSIONS: The sensitivity of PET in diagnosis of HCC was 55% compared to 90% for CT scanning, although only PET detected some tumors (including distant metastases). Well-differentiated and low tumor grades had lower activity on PET and correspondingly lower PET scores. PET imaging may help assess tumor differentiation and may be useful in the diagnosis and staging and prognostication of HCC as an adjunct to CT.

Radioguided surgical advancements for head and neck oncology.

Radioguided surgery is an innovative means by which a radionuclide is used to preoperatively image and intraoperatively visualize a structure of interest to the surgeon for excisional biopsy. This technology has allowed a cost-effective, highly specific means by which to locate a structure (usually a lymph node) and access it for pathologic analysis. The result of radioguided surgery is increased specificity in tissue obtained for biopsy, minimal access incisions, and the reduction of inpatient hospital utilization. Radioguided surgery should not be confused with radiosurgery, which is the stereotactic application of external beam radiation, usually for intracranial tumors.

Surveillance for recurrent head and neck cancer using positron emission tomography.

PURPOSE: Earlier detection of head and neck cancer recurrence may improve survival. We evaluated the ability of [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) to detect recurrence in a prospective trial using sequential PET scans. PATIENTS AND METHODS: Serial posttherapy FDG-PET was prospectively performed in 44 patients with stage III or IV head and neck cancer. PET was performed twice during the first posttreatment year (at 2 and 10 months after therapy) and thereafter as needed. After therapy, patients were grouped, based on tissue biopsies, into those who achieved a complete response (CR) and those who had residual disease (RD). Patients who achieved a CR were further grouped into those without evidence of disease and those who had recurrence by 1 year after completion of therapy. Disease status as determined by physical examination (PE), PET, and correlative imaging was compared. RESULTS: Eight patients were lost to follow-up and six had RD after therapy. Of the remaining 30 patients with a CR, 16 had recurrence in the first year after therapy. Five of these 16 patients had recurrence detected by PET only, four by PET and correlative imaging only, five by PE and PET only, and two by PE, correlative imaging, and PET. Only PET detected all recurrences in the first year. PET performed better than correlative imaging (P =.013) or PE (P =.002) in the detection of recurrence. CONCLUSION: PET can detect head and neck tumor recurrence when it may be undetectable by other clinical methods. FDG-PET permits highly accurate detection of head and neck cancer recurrence in the posttherapy period.

Initial evaluation of pulmonary abnormalities: CT-guided fine-needle aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography correlation.

Fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) can evaluate patients with new pulmonary lesions. CT-guided fine-needle aspiration (FNA) biopsy is a well-described method in the diagnosis of pulmonary lesions. In order to correlate results from these testing modalities, retrospective findings from FNA biopsies of pulmonary lesions are compared to concurrent FDG-PET scans. Files of the Saint Louis University Hospital were retrospectively searched for patients with CT-guided FNA biopsies of the lung during a consecutive 3-yr period. Patients were collected, and corresponding FDG-PET scans were identified. Only new pulmonary lesions presenting for initial evaluation were included. Findings were correlated. Forty patients with a total number of 41 CT-guided FNA biopsies of the lung and thoracic cavity had corresponding FDG-PET scans. The combined positivity of the two testing modalities, i.e., cases where both FNA and FDG-PET scan were positive, yielded a sensitivity of 100% (37/37). Four patients had infectious/inflammatory processes by CT-guided FNA biopsy that were FDG-PET-positive for malignancy. CT-guided FNA biopsies with FDG-PET scans of pulmonary lesions are important, complementary diagnostic tools which can contribute significantly to the management and treatment of pulmonary disease. Diagn. Cytopathol. 2000;22:92-96.

Primary and recurrent early stage laryngeal cancer: preliminary results of 2-[fluorine 18]fluoro-2-deoxy-D-glucose PET imaging.

PURPOSE: To evaluate the effectiveness of 2-[fluorine 18]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in the identification of early stage (T1-T2) primary and recurrent laryngeal cancer. MATERIALS AND METHODS: Twelve patients with T1 or T2 laryngeal cancer underwent imaging prospectively with PET. Seven patients had new disease, and five had recurrent disease. All patients underwent imaging prior to planned therapy and tissue biopsy. PET images were evaluated by using standardized uptake ratios and visual analysis. RESULTS: Histopathologic evidence of early stage cancer was documented in the 12 patients. One had a carcinoma in situ, nine had T1 tumors, and two had T2 tumors. Of the 12 patients, 10 had vocal cord tumors, one had a hypopharyngeal tumor, and one had a preepiglottic tumor. Eleven (92%) patients with early stage cancer had standardized uptake ratios indicative of malignancy (mean, 4.6; SD, 1.8; 95% CI, 1.2; range, 2.8-7.6). One had false-negative results (standardized uptake ratio = 2.3). Nine underwent CT, and results in the larynx were normal in seven and abnormal in two. CONCLUSION: FDG PET can be used to identify primary and recurrent early stage laryngeal cancer. It may be useful for follow-up after therapy.

Triple-technique (MR imaging, single-photon emission CT, and CT) coregistration for image-guided surgical evaluation of patients with intractable epilepsy.

Ictal and interictal single-photon emission CT (SPECT) play an increasingly important role in the surgical evaluation of patients with epilepsy. We present a method of coregistration of MR, SPECT, and CT images to correlate structural data (MR imaging), blood flow changes (SPECT), and location of subdural electrodes (CT) for patients undergoing image-guided surgical treatment of epilepsy. MR-SPECT root mean square (rms) mismatch distances were 2.1 to 2.5 mm, and MR-CT rms mismatch distances were 1.0 to 4.5 mm. Coregistration assisted in image-guided placement of subdural electrodes and in surgical resection of the suspected epileptogenic focus.

Correlation of CT-guided fine-needle aspiration biopsy of the liver with fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of metastatic hepatic abnormalities.

Imaging studies using the fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan have recently become available for patient neoplasia evaluation. Fine-needle aspiration (FNA) biopsy is a well-described diagnostic method for hepatic lesion evaluation. Correlation of these testing modalities in hepatic abnormalities has not been previously reported. Pathology files of Saint Louis University Hospital were retrospectively searched for patients with FNA biopsy of the liver. Thirty-one patients with a total of 32 FNA biopsies of the liver with corresponding FDG-PET scans were identified. Twenty-five patients had 25 cases of metastatic malignant neoplasia diagnosed by FNA biopsy. Of these cases, all but one had an FDG-PET scan positive for malignancy, yielding a sensitivity of 96% (24/25) for the FDG-PET scan. Combined positivity of the two testing modalities yielded a sensitivity of 100% (24/24). Seven patients did not demonstrate neoplasia by FNA biopsy, and the FDG-PET scan was negative in 6 of these 7 cases. The FDG-PET scan is an important imaging technique and, combined with FNA biopsy, can provide reliable diagnostic results and assist in the guidance of oncologic patient management.

Overexpression of MPS antigens by squamous cell carcinomas of the head and neck: immunohistochemical and serological correlation with FDG positron emission tomography.

Survival from advanced primary or recurrent Squamous Cell Carcinoma (SCC) of the head and neck (H&N) is poor. More accurate detection of primary tumors and recurrence may provide ways to improve survival. No standard serum tumor marker is routinely used for surveillance of SCC-H&N. In this paper, we evaluated the performance characteristics of the MPS-H tumor marker test for the quantitative measurement of "MPS-H" heat-generated immunoreactive proteins and assessed the clinical utility of this marker in the detection and monitoring of SCC-H&N. In approximately 92% of the subjects having no evidence of SCC-H&N, the MPS-H levels were lower than 15 ng/mL. In 76% of patients having SCC-H&N at various stages (T1-T4), the MPS-H level was > 15 ng/mL (range: 20-200 ng/mL). In addition, we found a statistically significant correlation between PET positive cases and high MPS-H serum levels in SCC-H&N patients with recurrent disease. These results suggest that MPS-H may provide an initial screening test that would allow for selective PET imaging in these patients. Furthermore, we found that there was greater expression of MPS-1 in tumors of higher histological grades. Thus, in tumors with more histological aggressiveness there is more MPS-1, indicating the potential usefulness of this marker in prognosis for SSC-H&N. Considering the immunohistochemical, serological, and FDG-PET data presented here, and the compelling need to expedite the early diagnosis of primary and recurrent epithelial malignancies of the head and neck, we are further evaluating the system of MPS antigens in a large patient population as a tool for the early serologic and histologic diagnosis of SCC-H&N.