(18)F-FDG PET and conventional imaging for assessment of Hodgkin's disease and non Hodgkin's lymphoma. An analysis of 193 patient studies.

UNLABELLED: The AIM of this study was to assess the diagnostic value of FDG-PET and conventional imaging (CI) in a large series of patient with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) at three time points during their course of disease. PATIENTS, METHODS: 169 consecutive lymphoma patients (69 HD; 100 NHL) were included. 193 FDG-PET studies were performed for staging at baseline in 42 cases, for post-therapeutic monitoring in 103, and for diagnosis of recurrence in 48 cases. Performance indices of sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and accuracy of metabolic FDG-PET and morphological CI were calculated. Differences in staging and diagnosis of residual or recurrent lymphoma were compared. RESULTS: FDG-PET changed staging in 36% of cases for staging at baseline, in 52% of cases for monitoring response to treatment, and in 29% for diagnosis of recurrence. FDG-PET staging results were confirmed in 80% for staging at baseline, in 74% for monitoring response to treatment, and in 50% for diagnosis of recurrence. FDGPET and CI differed significantly at monitoring response to treatment for sensitivity (0.91 versus 0.69; p < 0.02), specificity (0.90 versus 0.38; p < 0.00001), PPV (0.77 versus 0.42; p < 0.001), and accuracy (0.83 versus 0.55; p < 0.02). CONCLUSION: FDG-PET should be considered as the diagnostic modality of choice for post-therapeutic assessment of lymphoma patients and may be a reliable alternative to CI for staging at baseline and diagnosis of recurrence.

Assessment of cancer recurrence in residual tumors after fractionated radiotherapy: a comparison of fluorodeoxyglucose, L-methionine and thymidine.

UNLABELLED: This study evaluates the midterm follow-up of tumor and normal tissue uptake of deoxyglucose, thymidine and methionine after fractionated radiotherapy to assess cancer recurrence in residual tumors. METHODS: AH109A tumor-burdened rats were treated with one to eight doses of 5Gy 60Co radiation. Tissue distribution study with 18F-FDG, 3H-thymidine and 14C-methionine, double-tracer autoradiography with 18F-FDG and 14C-methionine, and single-tracer autoradiography with 14C-labeled deoxyglucose, thymidine and methionine were performed 6 days after the end of therapy. RESULTS: Dose response study shows a significant decrease of tumor uptake of all tracers after two and more doses, even in the case of later recurrence. Whereas 3H-Thd and 14C-Met tumor uptake was similar to that of normal muscle, 18F-FDG tumor uptake remains higher than that of muscle, even in the case of complete tumor cure. The irradiated muscle shows a higher 18F-FDG uptake than the nonirradiated muscle. Autoradiography after eight doses (100% tumor cure) reveals elevated 14C-DG tumor uptake to be ascribable to nonmalignant cellular elements, in particular to a macrophage layer at the rim of necrotic areas. Autoradiography after four and six doses (33% and 57% tumor cure) shows the highest methionine and thymidine uptake in viable cancer cells, whereas deoxyglucose uptake did not differ between viable cancer cells and macrophages. CONCLUSION: To detect and differentiate viable cancer cells in a residual tumor mass after radiotherapy, PET using 11C-methionine or 11C-thymidine may have some advantages over 18F-FDG, especially if the residual tumor includes larger areas of necrosis.

Increased metabolic activity in the thymus gland studied with 18F-FDG PET: age dependency and frequency after chemotherapy.

UNLABELLED: This study was designed to evaluate the age dependency of 18F-FDG uptake in the thymus and the frequency of PET confirmation of thymus hyperplasia after chemotherapy in cancer patients. METHODS: Whole-body FDG PET recordings of 168 patients were retrospectively examined for a retrosternal lesion in the anterior mediastinum that was attributable to the thymus. The patients were assigned to the following four groups: children with malignant lesions before the first therapy (group Ia; n = 15; mean age +/- SD, 11.9 +/- 3.7 y), children with malignant disease after chemotherapy (group Ib; n = 12; mean age, 10.3 +/- 5.0 y), adults with histologically confirmed malignant lymphoma before the first therapy (group IIa; n = 37; mean age, 43.9 +/- 16.7 y), and adult lymphoma patients 3 wk to 4 mo after chemotherapy (group IIb; n = 104; mean age, 40.9 +/- 14.6 y). RESULTS: Increased FDG accumulation in the thymus was seen in 11 patients (73%) of group Ia and 9 patients (75%) of group Ib. Thymus hyperplasia was found in 5 patients (5%) of group IIb. The eldest of these 5 patients was 25 y old. No increased FDG accumulation in the thymus was observed in any of the group IIa patients. In cases of visible FDG uptake in the thymus, standardized uptake values did not exceed 4. CONCLUSION: FDG accumulation in the thymus is a common finding in children and can occasionally be observed in young adults after chemotherapy. Knowledge of the characteristics of a typical retrosternal lesion in conjunction with the clinical history allows avoidance of diagnostic uncertainty and unnecessary procedures.

FDG-PET evaluation of retroperitoneal metastases of testicular cancer before and after chemotherapy.

We describe a patient whose primary tumor was a testicular teratocarcinoma predominantly composed of embryonal carcinoma. Before chemotherapy, the retroperitoneal metastases demonstrated heterogeneous, increased glucose metabolism as measured by 2-[18F]fluoro-2-deoxy-D-glucose and PET (FDG-PET). After chemotherapy, FDG uptake was reduced to normal values despite increased tumor volume. Histology revealed a pure mature teratoma. This observation suggests that further studies are needed to determine whether tumor differentiation of testicular teratocarcinoma metastases can be assessed by measuring glucose metabolism.

[Detection of impaired renal function: is the modern serologic marker cystatin C more accurate than the 99mTc-MAG3 clearance?]. / Nachweis der eingeschränkten Nierenfunktion: Ist der moderne serologische Marker Cystatin C der 99mTc-MAG3-Clearance überlegen?

AIM: Renal function is usually determined by means of creatinine-clearance, and of serum Cystatin C, the latter with increasing frequency. The present study analyses, whether the diagnostic accuracy of (99m)Tc-MAG(3) clearance is comparable to that of these modern serologic methods. PATIENTS, METHODS: 71 consecutive adult Caucasian patients (42 female, 29 male; age 50 +/- 16 yrs., range 20-83) who were referred to a nuclear medicine department for determination of bilateral renal function with (99m)Tc-MAG(3) were included. Following sufficient hydration, 10 ml of blood were taken for determination of Cystatin C and creatinine in serum prior to i.v. injection of the radiotracer. According to the recommendations of the National Kidney Foundation, glomerular filtration rate (GFR) was calculated from serum creatinine using either Cockcroft & Gault and Modification of Diet in Renal Disease (MDRD) study equation. These estimates of GFR served as reference. Cystatin C is a low molecular protein produced by all nuclear cells and is eliminated to 85 % by glomerular filtration. Analysis of (99m)Tc-MAG(3) clearance was performed by means of Bubeck's formula. RESULTS: Linear regression analysis produced Pearson's correlation coefficients of r = 0.68 and r = -0.69 for the comparison of either Cystatin C and (99m)Tc-MAG(3) clearance with the Cockcroft & Gault equation. The comparison of Cystatin C and (99m)Tc-MAG(3) clearance with MDRD study equation resulted in correlation coefficients of r = 0.755 and r = -0.77. None of these differences were significant. The exclusion of renal impairment or the detection of an at least moderate renal impairment revealed again no significant differences between Cystatin C and (99m)Tc-MAG(3) clearance. CONCLUSIONS: Cystatin C and (99m)Tc-MAG(3) clearance are equally suited to exclude renal impairment or to detect a relevant renal impairment. Differences between both procedures are more likely a result of the applied reference method.

[Change of 99m technetium-pertechnetate uptake by the thyroid under suppression (TcTus) induced by optimization of iodine supply in Germany]. / Anderung des 99mTechnetium-Pertechnetat-Uptakes der Schilddrüse unter Suppression (TcTUs) bei Verbesserung der Iodversorgung in Deutschland.

AIM: The present study deals with the change of the 99mTechnetium-pertechnetate thyroid uptake under suppression (TcTUs) in dependence on the urinary iodine excretion. METHODS: The study collective comprises 510 patients with euthyroid goiter (N = 91), with functional thyroid autonomy (N = 361) and with Graves, disease (N = 58), who were examined in the own thyroid ambulance between January 1995 and February 1997 and who presented with endogeneous or exogeneous TSH suppression. All patients received a quantitative thyroid scintigraphy with 99mTechnetium-pertechnetate and a measurement of the urinary iodine excretion. RESULTS: The TcTUs from the whole collective shows an inverse correlation to the urinary iodine excretion for the range of 0 to 500 micrograms iodine/g creatinine. The TcTUs remains constant on a low basal level for iodine excretion values over 500 micrograms iodine/g creatinine. Significant differences occur in dependence on the underlying disease. TcTUs is constantly low in patients with euthyroid goiter, independent of the iodine excretion value. The TcTUs is significantly increased in patients with functional thyroid autonomy or Graves' disease when iodine excretion is below 100 or 50 micrograms iodine/g creatinine respectively, but shows only minor changes when iodine excretion rises up to 500 micrograms iodine/g creatinine. When iodine excretion exceeds 500 micrograms iodine/g creatinine, the TcTUs of patients with thyroid autonomy drops down to a low basal level. CONCLUSION: The reference range of TcTUs for assessing functional thyroid autonomy will not change significantly when the iodine supply in Germany improves. The TcTUs of patients with functional thyroid autonomy might be up to one third higher under conditions of iodine deficiency than in iodine sufficiency. This should be taken into account, when therapeutical consequences were derived from the TcTUs. The TcTUs cannot be interpreted for iodine excretion values over 500 micrograms iodine/g creatinine.

Value of tumour marker S-100B in melanoma patients: a comparison to 18F-FDG PET and clinical data.

AIM: The S-100B protein is commonly used in the immunohistochemical diagnosis of malignant melanoma and its metastases and has recently been introduced as a tumor marker in peripheral blood, whereas 18F-FDG PET is currently the most sensitive in-vivo imaging method for melanoma staging. Thus, the efficiency of serum S-100B and 18F-FDG PET in the detection of metastatic disease in melanoma patients are compared. METHODS: Serum S-100B was measured with a commercially available immunoradiometric assay. As part of primary tumour staging whole-body positron emission tomography (PET) with 18F labeled fluorodeoxy-D-glucose (18F-FDG) was performed in 67 patients suffering from cutaneous melanoma with a tumour thickness > 0.75 mm and a Clark-level III-V. Final diagnosis based on histology, morphologic imaging results and/or clinical follow-up after at least six months. RESULTS: No evidence of disease was seen in 43 of 67 patients (64.2%), 11 patients (16.4%) presented with lymph node metastases, 13 patients (19.4%) had one or more distant metastases. Alltogether, 18 of 67 patients showed S-100B values > 0.2 microgram/l, including two patients without metastatic disease, 3 of 11 patients with lymph node metastases, and the 13 patients with distant metastases. One patient showed false-positive FDG-uptake in the mediastinum, but presented with S-100B values off curve. CONCLUSION: Our data indicate that serum S-100B determination might be helpful in identifying melanoma patients with distant metastases. In comparison to 18F-FDG PET, the value of serum S-100B for lymph-node staging is limited.

Radioisotope albumin flux measurement of microvascular lung permeability: an independent parameter in acute respiratory failure?

AIM: To evaluate the extent to which single measurements of microvascular lung permeability may be relevant as an additional parameter in a heterogenous clinical patient collective with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). METHODS: In 36 patients with pneumonia (13), non pneumogenic sepsis (9) or trauma (14) meeting the consensus conference criteria of ALI or ARDS double-isotope protein flux measurements (51Cr erythrocytes as intravascular tracer, Tc-99m human albumin as diffusible tracer) of microvascular lung permeability were performed using the Normalized Slope Index (NSI). The examination was to determine whether there is a relationship between the clinical diagnosis of ALI/ARDS, impaired permeability and clinical parameters, that is the underlying disease, oxygenation, duration of mechanical ventilation and mean pulmonary-artery pressure (PAP). RESULTS: At the time of study, 25 patients presented with increased permeability (NSI > 1 x 10(-3) min-1) indicating on exudative stage of disease, and 11 patients with normal permeability. The permeability impairment correlated with the underlying disease (p > 0.05). With respect to survival, there was a negative correlation to PAP (p < 0.01). Apart from that no correlations between the individual parameters were found. Especially no correlation was found between permeability impairment and oxygenation, duration of disease or PAP. CONCLUSION: In ALI and ARDS, pulmonary capillary permeability is a diagnostic parameter which is independent from clinical variables. Permeability measurement makes a stage classification (exudative versus non exudative phase) of ALI/ARDS possible based on a measurable pathophysiological correlate.

Improved diagnosis of advanced bone marrow metastases by means of radiolabeled antigranulocyte antibodies.

Assessment of bone marrow metastases using Tc-99m-labeled antigranulocyte antibodies and Tc-99m-labeled nanocolloids is discussed in osseous metastasizing breast cancer. A 53-year-old patient with bone metastases of breast cancer (pT2 pN1biv cM1) developed leukocytopenia WHO Grade III following polychemotherapy. Bone marrow scintigraphy with Tc-99m labeled nanocolloids and Tc-99m-labeled antigranulocyte antibodies revealed pronounced bone marrow infiltration as the cause. Comparing both procedures, the images with antigranulocyte antibodies showed a clearly better bone marrow image, considerably higher contrast and almost no superimposition of the liver over the spine. In osseous metastasizing breast cancer, scintigraphy with Tc-99m-labeled antigranulocyte antibodies enables assessment of metastases in the entire bone marrow.

Localization of active otosclerotic foci by tympano-cochlear scintigraphy (TCS) using correlative imaging.

High-resolution, tympano-cochlear scintigraphy (TCS) is a useful tool for visualizing changes in labyrinthine bone metabolism in active otosclerosis in vivo. But until now, the activity patterns have mostly been rather imprecisely ascribed to the labyrinthine structures; more exactly by means of high-resolution CT (HR-CT). Experimental studies on TCS using a human temporal bone model revealed that correlative imaging of X-ray photographs and the scintigrams or superimposition with masks of the temporal bone drawn from the X-rays can facilitate the localization of small foci of about 0.5-1 mm. Clinical applications of the visualization technique, combining functional with structural images, confirmed the benefit of this method, improving the accuracy in detection and localization of focal activity enrichment of the petrous bone in cases of active otosclerosis by means of TCS.

Computed tomography and 18F-FDG positron emission tomography for therapy control of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?

BACKGROUND: The aim of this study was to evaluate the accuracy of computed tomography (CT) and [(18)F]fluoro-deoxy-d-glucose positron emission tomography (FDG-PET) for prediction of progression-free survival of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) patients after completion of therapy. PATIENTS AND METHODS: CT and FDG-PET were performed in 40 HD, 17 indolent NHL and 44 aggressive NHL patients (29 women, 72 men; aged 41+/-14 years) in a median of 2 months after therapy. Progression-free survival was evaluated using the Kaplan-Meier method. Independent prognostic factors were identified by means of Cox proportional hazards model. RESULTS: CT imaging results were progressive disease (PD) in five, stable disease (SD) in 57, and partial response (PR) or complete remission (CR) in 39 patients. FDG-PET suggested residual lymphoma in 24 patients. Three-year progression-free survival rates after exclusion of five PD patients were: 100% (PET negative; CT: PR or CR), 81% (PET negative; CT: SD), 21% (PET positive; CT: SD) and 0% (PET positive; CT: PR). FDG-PET (P<0.0001) and bulky disease (P <0.05) were identified as independent prognostic variables. CONCLUSIONS: Among lymphoma patients with PR and SD on CT, FDG-PET discriminated those destined to progress into a low risk of < or =20% and a high risk for recurrence of > or =80%.

Dopamine transporter SPECT in patients with mitochondrial disorders.

BACKGROUND: Mitochondrial disorders may affect basal ganglia function. In addition, decreased activity of complex I of the mitochondrial electron transport chain has been linked to the pathogenesis of dopaminergic cell loss in Parkinson's disease. Objective : To investigate the dopaminergic system in patients with known mitochondrial disorders and complex I deficiency. METHODS: Dopamine transporter density was studied in 10 female patients with mitochondrial complex I deficiency by (123)I-FP-CIT (N-beta-fluoropropyl-2beta-carbomethyl-3beta-(4-iodophenyl)-nortropane) SPECT. RESULTS: No differences in (123)I-FP-CIT striatal binding ratios were observed and no correlation of the degree of complex I deficiency and striatal binding ratios could be detected. CONCLUSIONS: These data argue against the possibility that mitochondrial complex I deficiency by itself is sufficient to elicit dopaminergic cell loss.

An update on diagnostic methods in the investigation of diseases of the thyroid.

Iodine deficiency and iodine-deficiency disorders continue to be problems in several parts of Europe, requiring further improvements in the techniques employed in thyroid diagnosis, and particularly in the early diagnosis and risk assessment of autonomously functioning thyroid tissue. For the latter purpose, scintigraphy with technetium-99m pertechnetate under exogenous or endogenous thyroid-stimulating hormone (TSH) suppression provides the best results. Significant methodological improvements in laboratory tests have resulted from the application of new luminescent techniques and gene technology to thyroid function tests. Especially TSH measurement using second- or third-generation assays ensures diagnostic accuracy, so that the thyrotropin-releasing hormone (TRH) test is now almost always unnecessary. The differentiation of blocking and stimulating TSH receptor antibodies is relevant when discrepant results are obtained with respect to thyroid function. Determination of glycosaminoglycans in urine may become a helpful tool in the follow-up of endocrine ophthalmopathy. Some new imaging agents have recently been applied in the scintigraphy of thyroid diseases, such as octreotide, or in thyroid diagnosis, such as fluorodeoxyglucose. Both improve the detectability of metastases of thyroid cancer, especially if the radioiodine scan is negative.

PET-imaging in tumors of the reproductive trac.

There is increasing evidence that metabolic imaging with positron-emission tomography (PET) using fluor-18 labeled fluorodeoxyglucose (18F FDG) is highly accurate for in vivo detection of a variety of malignancies. This quality gives FDG-PET an important role in the detection of malignant tumors and their metastases as well as for differentiation of tumors of unknown etiology. In the male and female reproductive tract, whole body imaging with FDG-PET is in particular capable of visualizing lymph-node and distant metastases before these changes become apparent on conventional cross-sectional imaging modalities. According to the incidence of tumors in the reproductive tract, FDG-PET-imaging has been evaluated in prostate cancer, ovarian cancer, cervical and testicular cancer. The role of PET is discussed with respect to the current management of patients. The presented data indicate that FDG-PET is more accurate for lymph-node staging in cervical cancer and testicular cancer. In ovarian cancer, FDG-PET may be helpful for detection of tumor recurrence. The role of FDG-PET is questionable in prostate cancer, due to the low metabolic activity of this type of cancer. Carbon-11 labeled acetate and carbon-11 or fluor-18 labeled choline are more promising than FDG for detection of recurrence in prostate cancer. In all other tumors of the reproductive tract there is limited experience with PET for a final conclusion.

Experimental topographic study of high-resolution tympanocochlear scintigraphy using the human temporal bone model.

To determine the diagnostic value of tympanocochlear scintigraphy (TCS), which is still used for the visualization of alterations of labyrinthine bone metabolism due to active otosclerosis, resolution and detection limits were examined in a normal human temporal bone model. After incubation in technetium-99m-labeled diphosphonate solution, scintigraphic imaging showed the zygomatic process and the clivus as landmarks for fine structures of the petrous bone. For further differentiation, labyrinthine fine structures were marked with radioactive tracers of 0.5-1 mm2 each. High-resolution scintigraphic imaging gave two-point discrimination for structures as small as 2.5 mm apart. Localization of the activity patterns was improved by correlating imaging with X-ray photographs or by superimposition with masks of the prepared temporal bones drawn from the X-rays. The correlation of scintigraphic findings with X-ray photographs was found to provide a powerful method for improving the accuracy of localizing temporal bone metabolic changes as it is applicable clinically for studying the occurrence of small active otosclerotic foci.

MRI of active otosclerosis.

Our aim was to determine whether MRI reliably shows pathology in patients with active otosclerosis (otospongiosis). We studied five patients with clinical and audiometric signs of this disorder and positive findings on high-resolution CT and tympanocochlear scintigraphy. Contrast enhancement of otospongiotic lesions was found in all affected ears, and could be topographically related to demineralised otospongiotic foci on CT. In lesions in the lateral wall of the labyrinth MRI sometimes showed the pathology better than CT, where partial-volume effects could be troublesome.

Influence of urinary iodine excretion on thyroid technetium-99m pertechnetate uptake with and without TSH suppression: what happens when iodine supply increases?

This study examines how thyroid pertechnetate uptake with and without thyroid-stimulating hormone (TSH) suppression changes as a function of increasing iodine supply. This is of special interest in countries at the threshold of sufficient iodine supply, where thyroid scintigraphy plays a key role in thyroid examination, especially for the diagnosis of Plummer's disease. From 1995 to 1997, a total of 1069 patients with euthyroid goitre, Plummer's disease or Graves' disease were included in the study. All patients underwent thyroid examination including sonography, scintigraphy with technetium-99m pertechnetate, and determination of free triiodothyronine, free thyroxine, TSH and urinary iodine excretion. Iodine excretion in the range from 0 to 500 microg iodine/g creatinine showed an inverse correlation with thyroid pertechnetate uptake, but no correlation with TSH was observed. There was no correlation between thyroid pertechnetate uptake and iodine excretion when TSH stimulation was eliminated, with two exceptions: thyroid pertechnetate uptake was significantly increased for iodine excretion values below 50 and 100 microg iodine/g creatinine in patients with Graves' and Plummer's disease, respectively. When iodine excretion exceeded 500 microg iodine/g creatinine, pertechnetate uptake was reduced to a basal level independent of the TSH. In conclusion, the influence of TSH on the thyroid pertechnetate uptake seems to be secondary compared with the influence of the iodine supply. It can be concluded further that the reference range of thyroid pertechnetate uptake under TSH suppression will not change significantly when the iodine supply increases from conditions of mild iodine deficiency to iodine sufficiency. Thyroid pertechnetate uptake with and without TSH suppression cannot be reliably interpreted beyond an iodine excretion of 500 microg iodine/g creatinine.