Anti-thyroid peroxidase antibodies are associated with the absence of distant metastases in patients with newly diagnosed breast cancer.

BACKGROUND: The presence of thyroid peroxidase antibodies (TPOab) are reported to be associated with improved outcome among breast cancer patients. We evaluated the correlation between TPOab and diagnostic parameters among newly diagnosed breast cancer patients. METHODS: Three hundred and fourteen newly diagnosed patients with breast cancer, diagnosed and treated in Bethesda Essen between January 2002 and June 2006, were included in this study; 258 (82.2%) without TPOab (≤100 IU/mL) and 56 (17.8%) with TPOab (>100 IU/mL). Blood analysis was performed to measure serum levels of carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA-15-3), free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and TPOab by radioimmunoassay. Data regarding age, tumor size, grading, TNM classification, receptor status, lymph node, and distant metastases were collected and analyzed from patient reports. Statistics were performed using Pearson's χ2-test and logistic regression analysis. RESULTS: There were no incidences of distant metastasis among 56 patients with TPOab, whereas 17 (6.6%) of 258 cases without TPOab displayed distant metastases (p=0.04). Logistic regression showed an inverse association of TPOab with CA-15-3 and CEA levels (p<0.001, respectively). Both groups, with and without TPOab, revealed no significant differences with respect to age, tumor size, grading, TNM classification, fT3, fT4, and receptor status. TPOab positive patients had higher TSH levels (2.55±3.58), compared to TPOab negative cases (1.20±1.15) (p<0.001). CONCLUSIONS: TPOab occurrence is associated with significantly lower frequency of distant metastases in breast cancer. TPOab level inversely correlates with the conventional tumor markers CA-15-3 and CEA.

The effect of excisional biopsy on the accuracy of sentinel lymph node mapping in early stage breast cancer: comparison with core needle biopsy.

Despite the successful application of sentinel node mapping in breast cancer patients, its use in patients with a history of previous excisional biopsy of the breast tumors is a matter of controversy. In the present study we evaluated the accuracy of sentinel node biopsy in this group of patients and compared the results with those in whom the diagnosis of breast cancer was established by core needle biopsy. Eighty patients with early stage breast carcinoma were included into our study. Forty patients had a history of previous excisional biopsy and the remainder 40 had undergone core needle biopsy. Intradermal injections of 99mTc-antimony sulfide colloid as well as patent blue were both used for sentinel node mapping. Sentinel nodes were harvested during surgery with the aid of surgical gamma probe. All patients underwent standard axillary lymph node dissection subsequently. Detection rate was 97.5 per cent for both groups of the study. Number of detected sentinel node during surgery was not significantly different between groups. False negative rate was 0 per cent for both groups of the study. In conclusion sentinel node biopsy is reliable in patients with previous history of excisional biopsy of the breast tumors and has a low false negative rate.

How to apply the evidence-based medicine concept to nuclear medicine diagnostic studies -- a review.

Evidence-based medicine (EBM) is defined as using the best available evidence for managing patients in daily healthcare practice. Although this approach has been applied successfully in many medical fields, it has not been addressed fully in the radiological discipline in general and nuclear medicine in particular. In this review, the concept of EBM has been introduced briefly and four steps of EBM practice have been explained. Asking answerable questions and finding the best evidence that constitutes the first two parts of EBM practice are explained in brief. The next two steps (appraising the available evidence and applying the best evidence) are explained in more detail. Since the bulk of nuclear medicine studies are of a diagnostic nature and most of the daily practice of a nuclear medicine specialist is involved in diagnosis, we have focused on the diagnosis studies. Systematic reviews are also explained to some extent. Appraisals of other kinds of study, such as interventional or prognosis studies, are not included in this review.

Application of technetium-99m-sestamibi in differentiation of active from inactive pulmonary tuberculosis using a single photon emission computed tomography method.

OBJECTIVE: We studied the usefulness of 99mTc-methoxyisobutylisonitrile (MIBI) scintigraphy for differentiation between active and inactive pulmonary tuberculosis. METHODS: Thirty-six patients (aged 27-82 years, 16 males and 20 females) were included in our study. Each patient was injected with 740 MBq (20 mCi) 99mTc-MIBI and both planar and single photon emission computed tomography (SPECT) imaging were performed 15 and 60 min after injection. Twenty-four patients had active pulmonary tuberculosis (proven by sputum culture), and the remainder 12 had negative sputum culture. Semiquantitative as well as visual assessments were done on all sets of images. RESULTS: All of the 12 patients in the control group had negative scintigraphy on both planar and SPECT images. Twenty patients with active pulmonary tuberculosis had positive 99mTc-MIBI scintigraphy on planar images (sensitivity of 87.5%). SPECT images were positive in 23 patients with active pulmonary tuberculosis (sensitivity of 95.8%). Both semiquantitative and visual assessment of planar and SPECT images showed statistically significant differences between active and inactive pulmonary tuberculosis patients (P<0.001). Comparison of 15 and 60 min image sets did not show any statistically significant difference (P=0.956 and 0.457 for planar and SPECT images, respectively). CONCLUSION: 99mTc-MIBI has significant uptake in the active tuberculosis lesions and can be used to differentiate between active and inactive tuberculosis. The SPECT method is especially useful because of its higher sensitivity.

Long-Acting Somatostatin Analog Therapy Differentially Alters 68Ga-DOTATATE Uptake in Normal Tissues Compared with Primary Tumors and Metastatic Lesions.

Synthetic somatostatin analogs have been posed as a potential source of error in somatostatin receptor imaging through interference with tumor detection; however, experimental models and clinical studies have shown a complex mechanism of the effect of octreotide on tumors. The aim of this study was to assess whether 68Ga-DOTATATE uptake before treatment with long-acting somatostatin analogs differs from that after treatment. Methods: Thirty patients (15 men; age [mean ± SD], 64.6 ± 13.4 y) who had intermediately differentiated to well-differentiated neuroendocrine tumors and who underwent 68Ga-DOTATATE PET/CT scanning before and after receiving long-acting repeatable octreotide (Sandostatin LAR) were included in the study. The SUVmax and SUVmean of healthy target organs, residual primary tumor, and up to 5 lesions with the highest SUVmax in each organ were compared before and after octreotide treatment. Results: The mean time interval between the 2 68Ga-DOTATATE studies was 9.6 ± 7.2 mo, and the mean time gap between the last Sandostatin LAR injection and the second 68Ga-DOTATATE study was 25.1 ± 14.8 d. The pretreatment mean SUVmax and SUVmean were both significantly higher in the thyroid, liver, and spleen (P < 0.05) than the values measured after the administration of Sandostatin LAR. No significant differences were found among the uptake indices for residual primary tumor or any metastatic lesions in the liver, bone, lung, or lymph nodes before and after Sandostatin LAR administration (P > 0.05). Conclusion: Long-acting octreotide treatment diminished 68Ga-DOTATATE uptake in the liver, spleen, and thyroid but did not compromise tracer uptake in residual primary tumor and metastatic lesions. These findings have a direct impact on the interpretation of 68Ga-DOTATATE PET/CT scans.

Multicenter study evaluating extraprostatic uptake of 11C-choline, 18F-methylcholine, and 18F-ethylcholine in male patients: physiological distribution, statistical differences, imaging pearls, and normal variants.

AIM: The aim of the study was to evaluate the visceral localization of the three most commonly used choline-based radiotracers (C-choline, F-methylcholine, and F-ethylcholine) with the aim of analyzing uptake in metabolically and anatomically disease-free patients. MATERIALS AND METHODS: A total of 1250 standardized uptake values (SUVmax, SUVmean) were analyzed in 45 anatomical regions in 45 patients (15 patients with C-choline, 15 with F-methylcholine, and 15 with F-ethylcholine). These patients were selected from a cohort of 3721 choline PET/computed tomography studies performed at three teaching hospitals over a period of 10 years. They had no evidence of metabolically active primary disease, metastatic disease, or altered morphology on the computed tomography component of the study or any evidence of disease elsewhere on other imaging modalities. The sites of primary disease (prostate and seminal vesicles) were excluded from evaluation. RESULTS: No adverse effect was documented when using the three tracers. Visceral localization was the same for all three tracers. Viscera with a statistical difference in intensity of uptake included the choroid plexus (P=0.0001), occipital lobe (P=0.014), parietal lobe (P=0.008), cerebellum (P=0.003), parotid gland (P=0.005), submandibular gland (P=0.001), tonsils (P=0.001), thyroid (P=0.0001), lungs (P=0.001), aorta (P=0.001), pulmonary artery (P=0.0001), liver segments I (P=0.005), III (P=0.005), IVB (P=0.03), and V (P=0.01), spleen [hilum (P=0.0009), body (P=0.0001)], pancreas [head (P=0.0001), body (P=0.01), tail (P=0.002)], esophagus (P=0.001), stomach (P=0.0001), duodenum (P=0.0002), large intestine (P=0.008), and rectum (P=0.0001). Elsewhere, no statistical difference was observed. Excreted activity was noted in the kidneys and bladder. CONCLUSION: This study demonstrates that the visceral localization of C-choline, F-methylcholine, and F-ethylcholine in disease-free patients is similar. Depending on the tracer uptake pattern, the viscera can be divided into two distinct categories: those with a statistically significant difference in uptake and those with no difference in uptake. The study outlines the range of SUVs for various organs for the three tracers and identifies some of the potential pitfalls in the evaluation of 'nonavid' but clinically significant presentation of different disease entities.

BAY 1075553 PET-CT for Staging and Restaging Prostate Cancer Patients: Comparison with [18F] Fluorocholine PET-CT (Phase I Study).

PURPOSE: (2RS,4S)-2-[(18)F]Fluoro-4-phosphonomethyl-pentanedioic acid (BAY1075553) shows increased uptake in prostate cancer cells. We compared the diagnostic potential of positron emission tomography (PET)-X-ray computed tomography (CT) imaging using BAY1075553 versus [(18)F]f luorocholine (FCH) PET-CT. PROCEDURES: Twelve prostate cancer patients (nine staging, three re-staging) were included. The mean prostate-specific antigen in the primary staging and re-staging groups was 21.5 ± 12 and 73.6 ± 33 ng/ml, respectively. Gleason score ranged from 5-9. In nine patients imaged for pre-operative staging, the median Gleason score was 8 (range, 7-9). PET acquisition started with dynamic PET images in the pelvic region followed by static whole-body acquisition. The patients were monitored for 5-8 days afterward for adverse events. RESULTS: There were no relevant changes in laboratory values or physical examination. Urinary bladder wall received the largest dose equivalent 0.12 mSv/MBq. The whole-body mean effective dose was 0.015 mSv/MBq. There was a significant correlation between detected prostatic lesions by the two imaging modalities (Kappa = 0.356, P < 0.001) and no significant difference in sensitivity (P = 0.16) and specificity (P = 0.41). The sensitivity and specificity of PET imaging using BAY1075553 for lymph node (LN) staging was 42.9 % and 100 %, while it was 81.2 % and 50 % using FCH. The two modalities were closely correlated regarding detection of LNs and bone metastases, although BAY1075553 failed to detect a bone marrow metastasis. Degenerative bone lesions often displayed intense uptake of BAY1075553. CONCLUSIONS: BAY1075553 PET-CT produced no adverse effects, was well tolerated, and detected primary and metastatic prostate cancer. FCH PET-CT results were superior, however, with respect to detecting LN and bone marrow metastases.

Thyroglobulin increment after thyroid hormone withdrawal is a reliable indicator for the detection of significant remnants or metastases in patients with differentiated thyroid carcinoma.

Serum thyroglobulin (Tg) measurement has a pivotal role in the management of differentiated thyroid carcinoma (DTC). Serum Tg increment after thyroid hormone discontinuation seems to be a better predictor of tumor recurrence, however, minimal Tg increment may not be a specific marker. This study tries to evaluate the importance of different levels of Tg increment after thyroid hormone discontinuation. Fifty-five patients (46 females and 9 males with mean age of 41.40 yrs) with DTC, treated with total or subtotal thyroidectomy and radioiodine-131 ((131)I) were studied. Ninety-one per cent of the patients had papillary carcinoma. Serum Tg and thyroid stimulating hormone (TSH) were measured using high sensitive IRMA assays during thyroxine (T4) suppression and after discontinuation of T4 treatment. The mean time interval between Tg on T4 and off T4 was 110.29+/-53.43 days and less than 180 days in all patients. Serum Tg level was increased >or= 1 ng/ml in 25 patients after discontinuation of T4. Of these patients, 17 had metastatic disease or a detectable thyroid remnant. Of 16 patients with unchanged Tg (-1or= 7 ng/ml had residual disease or metastases. If DeltaTg was unchanged or decreased, the negative predictive value was 83.3%. The sensitivity of WB(131)IS was 63.6% for the detection of thyroid remnant or metastases. Our study indicates that DeltaTg is a more reliable indicator of remnant disease than on T4-Tg or off T4-Tg levels.

Easy-to-use online software package for internal dose assessment after radionuclide treatment in clinical routine.

BACKGROUND: Internal dose assessment after radionuclide therapy is usually performed using home-made software packages. The dose assessment includes image registration, region-of-interest drawing, time-activity curve generation, and manual calculation of residence times followed by dose calculation with the OLINDA/MIRD software. The drawback of these methods is that several steps have to be performed using various software products possibly installed on different workstations. The aforementioned approaches are error-prone as well as difficult and time-consuming. In this article, we present a commercial software package that implements all the required dose calculation steps in 1 application, which greatly facilitates the internal dose assessment. METHODS AND RESULTS: The workflow of the newly developed software package "Hybrid Dosimetry" proceeds from automatic image registration to region-of-interest drawing, followed by time-activity curve fitting and dose calculation according to the MIRD method. The software is available online and can be run on independent computers using images in the common DICOM format. We used the package for internal dosimetry of 8 patients treated with Lu-DOTATATE and compared the results with manual dose calculation. CONCLUSIONS: The online software package presented is platform independent and allows fast dose calculations. The results obtained with the new package were in perfect agreement with manual methods.

Impact of 18F-choline PET/CT in prostate cancer patients with biochemical recurrence: influence of androgen deprivation therapy and correlation with PSA kinetics.

UNLABELLED: We evaluated the potential of (18)F-fluoromethyldimethyl-2-hydroxyethyl-ammonium (FCH) PET/CT in the detection of recurrent disease or distant metastases and correlated its diagnostic accuracy with prostate-specific antigen (PSA) levels in prostate cancer patients with biochemical evidence of recurrence. Furthermore, the influences of androgen deprivation therapy (ADT) and its duration on (18)F-FCH PET were assessed in this study. METHODS: This prospective study included 250 prostate cancer patients with PSA relapse who underwent (18)F-FCH PET/CT. At the time of (18)F-FCH PET/CT imaging, the mean PSA level was 46.9 ± 314.7 ng/mL and 55.2% (138/250) of patients were receiving ADT. Overall, ADT was performed on 67.2% (168/250) of patients after initial treatment. Imaging was performed on an integrated PET/CT system. Acquisition started 1 min after intravenous injection of (18)F-FCH (4.07 MBq/kg of body weight) with dynamic PET images in the pelvic region during 8 min (1 min/frame) followed by a static semi-whole-body acquisition. The final diagnosis of positive PET lesions was based on histopathology or a consensus of clinical findings, additional imaging, or follow-up imaging modalities. RESULTS: (18)F-FCH PET/CT was able to correctly detect malignant lesions in 74% (185/250) of patients but was negative in 26% (65/250). In 28% of patients, only 1 lesion was detected (69/250); from these, 65.2% (45 patients) had a local recurrence, 18.8% (13 patients) a single lymph node, and 15.9% (11 patients) a solitary bone metastasis. The sensitivity of the (18)F-FCH PET was significantly higher (P = 0.001) in patients with ongoing ADT (85%; confidence interval, 80%-91%) than in patients without ADT (59.5%; confidence interval, 50%-69%). (18)F-FCH PET sensitivity was 77.5%, 80.7%, 85.2%, and 92.8% for the trigger PSA levels of more than 0.5, 1.0, 2.0, and 4.0 ng/mL, respectively. Scan sensitivity was 33% in patients with a trigger PSA level of less than 0.3 ng/mL and 77% in patients with a trigger PSA level of greater than 0.3 ng/mL, respectively (P = 0.001). Using a binary logistic regression analysis model, we showed trigger PSA and ADT to be the only significant predictors of positive PET findings. CONCLUSION: (18)F-FCH PET/CT proved its potential as a noninvasive 1-stop diagnostic modality enabling us to correctly detect occult disease in 74% of patients and to differentiate localized from systemic disease. In patients with biochemical recurrence, it also guides to an optimal treatment approach after initial treatment. Trigger PSA and ADT are the 2 significant predictors of (18)F-FCH-positive PET lesions. ADT seems not to impair (18)F-FCH uptake in hormone-refractory prostate cancer patients.

Supplementary value of functional imaging in forensic medicine.

AIM: The aim of this study is to evaluate the role of functional imaging for forensic purposes. METHODS: We reviewed a few outpatient cases that were sent to our department for examination after traumatic events and one case with neuropsychic disturbances. RESULTS: Functional imaging showed signs of traumatic lesions in the skeletal system, of brain metabolism and of renal failure. CONCLUSION: Functional disturbances following traumatic events are in some cases more important than morphological abnormalities. Targeted scintigraphic examinations could be applied for visualisation of traumatic lesions or evaluation of functional disturbances caused by traumatic events. These examinations can be used as evidence in the courtroom.

Prognostic significance of the standardized uptake value of pre-therapeutic (18)F-FDG PET in patients with malignant lymphoma.

Metabolic imaging with F-18-fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) is widely used for staging and treatment evaluation of malignant lymphoma. To date, only a few studies have indicated that lower glucose metabolism measured by 18F-FDG PET before or early in the course of treatment of malignant lymphoma is associated with a favorable outcome. The aim of this study was to assess the prognostic capability of the 18F-FDG PET maximum standardized uptake value (SUVmax), a semiquantitative measurement of glucose metabolism, at the time of diagnosis of malignant lymphoma. We retrospectively analyzed data from 69 patients (median age: 61 and range 23-80) with malignant lymphoma (22 patients with Hodgkin's disease [HD] and 47 patients with Non-Hodgkin's lymphoma [NHL]) who had not received treatment before 18F-FDG PET imaging. Metabolic remission according to PET results was observed after chemotherapy in 50 patients (72.5%), while progressive disease or relapse was diagnosed in 19 patients (27.5%). Clinical follow-up revealed relapse in 4/50 patients with prior metabolic remission. A significantly lower (P<0.01) baseline SUVmax level (median: 4.6 and range 1.5-12.9) was found in patients with subsequent metabolic and clinical response than in those with progressive or relapsing disease (median SUVmax 10.4, range 2.0-17.9). Thirty-seven of thirty-nine patients with baseline SUVmax<7.4 achieved long-lasting remission after completion of chemotherapy (median follow-up: 28 months, range 4-112 months). Within this group with favorable outcome, there were no significant differences between SUVmax values in HD and NHL. A heterogeneous outcome was noted in 25 patients with a SUVmax≥7.4 and ≤12.9 at diagnosis, with 16 patients experiencing disease progression or relapse and nine patients extended remission. The five patients with SUVmax>12.9 showed disease progression at follow-up. Semiquantitative measurement of glucose metabolism (SUVmax) by 18F-FDG PET at diagnosis is a predictor of outcome of patients with malignant lymphoma.

Fully automated 3D basal ganglia activity measurement in dopamine transporter scintigraphy (Spectalyzer).

OBJECTIVES: Semiquantitative evaluation of tracer uptake in basal ganglia is superior to visual assessment of images in dopamine transporter (DAT) scintigraphy especially in follow-up of the patients. Manual drawing of regions of interest (ROIs) in two-dimensional (2D) transaxial slices of the single photon emission computed tomography (SPECT) datasets leads to a large inter- and intra-reader variability, while being time consuming. Our aim was to investigate a technique that extracts 3D ROIs in a fully automated fashion and thus might provide reproducible user-independent results allowing better follow-up control and large-scale clinical studies. METHODS: The highest activity of 123IFP-CIT is expected in the basal ganglia. The proposed method (Spectalyzer) uses the following steps to localize this maximum and extract the ROIs in 3D: (1) Dithers the SPECT volume to obtain a 3D volume with binary only. (2) Models the obtained point distributions as two multivariate Gaussian distributions and estimated their parameters using the expectation maximization algorithm. (3) Using the original SPECT activity values, thresholding is performed using a fixed percentage of maximum activity as a parameter to obtain the 3D ROIs. (4) A reference volume in the occipital region is automatically found based on the location of the two ROIs. (5) From the 3D ROIs, statistical information like mean and median activity and the volume is extracted, relative to the activity in the reference region. The resulting values are compared with values from manual 2D ROIs. Further validation is performed by means of an anthropomorphic striatal phantom. RESULTS: The method was evaluated on 12 SPECT volumes including anthropomorphic striatal phantoms. In all cases the two basal-ganglia were successfully localized and the 3D ROIs estimated, with perfect reproducibility. The obtained values for the mean activity showed the same trend with the values obtained manually and also with the results of the 2D semiautomatic software, but without the substantial inter- and intra-reader variations. CONCLUSIONS: The proposed method is successful in finding the 3D ROIs and performing the subsequent measurements automatically. It is proposed as an automatic reproducible approach for semiquantitative analysis of DAT scintigraphy.