[Significance of PET and integrated PET/CT in the diagnostics of occult primary tumors]. / Stellenwert von PET und integriertem PET/CT in der Diagnostik des CUP-Syndroms.

BACKGROUND: In the last years (18)F-FDG-positron-emission-tomography (PET) worked satisfactorily as helpful auxiliary method in order to verify recurrency of head and neck tumors and to detect primary tumors in case of CUP syndrome especially when CT and MR imaging failed to identify the tumor accurately. Fusion of FDG hypermetabolism in PET scan and anatomical structures is achieved by integrating positron emission tomography with CT and provides improvement also in case of CUP syndrome. This retrospective study shows 47 patients with neck metastases where PET or PET/CT helped to detect primary tumor site. PATIENTS: In a retrospective investigation 49 PET studies of 47 patients with CUP syndrome were analyzed. RESULTS: 9 cases had positive PET findings, 1 case false-positive. 5 cases were false-negative. In 40 PET studies there couldn't be found any sign of suspicious FDG hypermetabolism. CONCLUSION: PET and PET/CT deliver a certain improvement in localization of primary tumor site and therapeutical strategy.

[The integrated PET/CT: technological advance in diagnostics of head and neck recurrencies and CUP?]. / Das integrierte PET/CT: Technischer Fortschritt in der Diagnostik von Kopf-Hals-Karzinom-Rezidiven und CUP?

BACKGROUND: In the last years (18)F-Fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) worked satisfactorily as auxiliary method in order to show recurrency of head and neck tumors and to detect primary tumors in case of CUP especially when CT and MR imaging failed to identify the tumor accurately. The correlation of FDG hypermetabolism and anatomical structures is now provided by a new technology which is integrating PET and CT: Integrated PET/CT represents a new technical development, which combines the advantages of CT and PET. PATIENTS: In a retrospective investigation 84 non selected PET/CT studies of 83 patients with recurrent head and neck disease and CUP were critically analyzed. RESULTS: 33 cases had positive PET findings. 5 of these 33 cases showed false-positive findings. In 51 PET studies there was not found any sign of suspicious FDG hypermetabolism. CONCLUSION: Integrated PET/CT delivers substantial progress in detecting tumor localization. False positive findings have to be considered and therefore indications should be strictly limited to special cases of head and neck tumor recurrency, cases with complex anatomical sites and CUP.

131 I-cG250 monoclonal antibody immunoscintigraphy versus [18 F]FDG-PET imaging in patients with metastatic renal cell carcinoma: a comparative study.

The aims of this study were to establish the percentage of metastatic renal cell carcinoma (RCC) lesions detected by radioimmunoscintigraphy (RIS) with the chimeric monoclonal antibody 131I-cG250 versus positron emission tomography (PET) with 18F-labelled deoxyglucose ([18F]FDG), and to evaluate the use of these radionuclide imaging modalities compared with routinely used imaging techniques. Twenty patients with metastatic RCC disease were examined with [18F]FDG-PET and 131I-cG250 RIS within 1 week. Total body gamma camera images were obtained up to 120h after injection of 232MBq 131I-cG250. Total body PET scanning was performed 45-60 min after intravenous injection of 370MBq [18F]FDG. Nuclear medicine techniques were compared to routine imaging procedures. Routine imaging modalities revealed a total of 79 metastases. [18F]FDG-PET and 131I-cG250 RIS detected 33 previously unknown metastases, of which 32 were [18F]FDG positive and seven were 131I-cG250 positive. Of the 112 tumour lesions that were documented, [18F]FDG-PET detected 69% (77 out of 112), whereas 131I-cG250 RIS detected only 30% (34 out of 112). In conclusion, [18F]FDG-PET is superior to 131I-cG250 RIS in detecting metastases in patients with metastatic RCC, and therefore seems a promising tool for (re)staging patients with RCC. The usefulness of RIS with a diagnostic dose of 131I-cG250 seems to be restricted to selecting patients for radioimmunotherapy with 131I-cG250.

[Radiosynovectomy for the treatment of rheumatoid arthritis of the elbow joint]. / Die Radiosynoviorthese zur Therapie der rheumatoiden Arthritis des Ellenbogengelenks.

UNLABELLED: The aim of this retrospective study was to evaluate the efficacy of radiosynovectomy (RSO) in patients with rheumatoid elbow arthritis. PATIENTS AND METHODS: 40 joints of 31 patients were evaluated. At the time of therapy, patients had been suffering from elbow arthritis for 17.5 months (2-72 months). 95% of the joints (n = 38) had severe daily pain or continuous pain, 97.5% (n = 39) had moderate to severe limitation of the mobility and 10% (n = 4) had severe swelling. RSO was performed by intraarticulär injection of 74 MBq colloidal rhenium-186 and 15 mg triamcinolonehexacetonide. Before and six to 26 months after therapy (median follow-up 14.7 months) severity of the patients pain, mobility and swelling (transferred to a scoring system) were determined with a standardised questionnaire. A clinical re-evaluation, along with an orthrosonographical follow-up was performed in 28 joints. RESULTS: A "good to very good" overall long-term response was achieved in 80% (n = 32) of the treated joints and a temporary response in 10% (n = 4). Only 10% (n = 4) had a non-satisfactory response due to advanced articular destruction. The range of motion for flexion-extension increased from 103.8 +/- 20.0 degrees to 144.0 +/- 12.8 degrees (p < 0.001). The respective scores for articular pain, impaired mobility and swelling decreased significantly (pain from 3.15 to 0.82, impaired mobility from 3.15 to 0.82, swelling from 2.40 to 0.65; p < 0.001). No deterioration or complication occurred. The effects lasted throughout the entire follow-up time for 36 joints (90%). CONCLUSION: For patients with rheumatoid involvement of the elbow joint, radiosynovectomy results in a significant decrease of articular pain and improvement of objective parameter, i.e. joint mobility. Thus, radiosynovectomy represents a feasible and effective therapeutic option for elbow arthritis.

Absence of somatostatin receptor expression in vivo is correlated to di- or tetraploid 1p36-deleted neuroblastomas.

BACKGROUND: Poor prognosis in childhood neuroblastoma is associated with deletions of chromosome region 1p36 and di/tetraploid DNA content. PROCEDURE: Forty-six patients with histopathologically proven neuroblastoma were investigated for in vivo expression of somatostatin receptors (SR) by 111In-pentetreotide scintigraphy. All tumors were analyzed for cytometric DNA content and chromosome 1p36 integrity. RESULTS: SR expression was detected in 28 tumors (61%) and correlated with young age, localized clinical stage, and favorable outcome. Fourteen tumors showed deletion at chromosome 1p36, thirteen of which did not show SR expression (P< 0.001). A triploid DNA content was correlated with the presence of SR (23 of 25, P< 0.001). No tumor with deletion of chromosome 1p36 and di/tetra DNA content showed SR expression (chi2 = 29.88, d.o.f. = 2, P < 0.001). CONCLUSIONS: We conclude that SR expression is related to genetic features of prognostic significance. This may be assessed with a minimally invasive scintigraphic method.

Clinical relevance of positron emission tomography (PET) in treatment control and relapse of Hodgkin's disease.

BACKGROUND: In Hodgkin's disease accurate restaging is important to assess treatment results and may eventually provide a basis for further therapeutic strategies. A typical dilemma after treatment of Hodgkin's disease with radiographically persistent lymphoma is the differentiation between sterilized residual mass and viable tumor. Positron emission tomography (PET) has been described as a reliable tool to identify active lymphoma. Aim of the present study was to assess the accuracy and clinical relevance of PET for treatment control and in the situation of a suspected relapse of Hodgkin's disease. PATIENTS AND METHODS: 63 patients (32 men, 31 women, mean age 41.5 years) with Hodgkin's disease were investigated with FDG-PET. In 51 patients 63 PET studies were performed as a treatment control (group 1) after primary therapy. 17 patients (5 of whom preexamined in group 1) underwent 18 PET scans for confirmation of suspected relapse (group 2). PET was performed with a dedicated whole-body ring scanner. In a retrospective analysis, all FDG-PET scans were compared with conventional imaging methods and related to the final diagnosis obtained by histology and/or clinical follow-up (mean 22.4 months). RESULTS: Group 1: FDG-PET showed an accuracy of 91%, whereas the accuracy of conventional imaging was 62%. Group 2: The accuracy for PET was 83% and 56% for conventional imaging. CONCLUSION: The present data suggest that PET is a sensitive and reliable tool for detection of involved areas of active Hodgkin's disease. The accuracy of PET for restaging purpose seems to be superior than conventional imaging.

Whole body positron emission tomography in the treatment of Hodgkin disease.

BACKGROUND: In Hodgkin disease (HD), accurate assessment of the extent of disease is essential because it provides the basis for different treatment strategies. In addition to conventional imaging methods (CIM), positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) may permit reliable differentiation between lymphoma and nonmalignant tissue and thus improve determination of the stage of the disease. The aim of the current study was to assess the clinical value of FDG-PET for primary staging, treatment monitoring, and assessment in a suspected case of recurrent HD. METHODS: Eighty-one patients with HD underwent 106 FDG-PET studies using a dedicated whole body PET ring scanner. In 25 patients PET was part of the primary staging, 63 PET studies were undertaken for treatment monitoring after the completion of treatment, and in 18 patients PET was performed in cases of suspected recurrence of HD. PET scans were compared with CIM and verified histologically and/or by follow-up evaluation (mean follow-up duration, 20.4 months). RESULTS: With regard to primary staging, in a patient to patient analysis, both PET scans and CIM were positive (i.e., showed pathologic foci indicative of HD) in 24 of 25 cases. In a staging-relevant lesion to lesion analysis, accuracy in the determination of the stage of disease was 96% for PET versus 56% for CIM. PET led to a lower stage classification in 28% and a higher stage classification in 12% of cases, compared with the stage assumed with CIM. With regard to treatment monitoring, PET showed an accuracy of 91% compared with 62% for CIM. The negative predictive value of PET was 96%. With regard to suspected recurrence, PET findings were true-positive in 10 of 12 PET scans and true-negative in 5 of 6 PET scans, resulting in accuracy of 83%, which compares favorably with the accuracy rate of 56% for CIM. CONCLUSIONS: It may be concluded that FDG-PET is capable of determining the stage of HD with great accuracy and is capable of correctly detecting manifestations of HD in treatment monitoring and cases of suspected recurrence, in which CIM occasionally result in equivocal findings. The results of the current study suggest that FDG-PET should become a routine tool in the staging/restaging of HD.

Combined (111)In-pentetreotide scintigraphy and (123)I-mIBG scintigraphy in neuroblastoma provides prognostic information.

BACKGROUND: High-affinity somatostatin receptors (SRs) have been characterized in neuroblastomas and may be used as target structures for in vivo detection of SR. PROCEDURE: Eighty-eight children with histologically proven neuroblastoma were investigated at diagnosis or relapse by (123)I-mIBG and (111)In-pentetreotide scintigraphy. All tumors were investigated for MYCN copy number, chromosome 1p36 status, and 68/88 also for DNA content, followed for a median follow-up of 35 months (range 1-88 months). RESULTS: SR expression was detected in 56/88 tumors and (123)I-mIBG showed positivity in 83/88. (111)In-pentetreotide was less sensitive in detecting tumor tissue than was (123)I-mIBG (64% vs. 94%, P = 0.005). Survival (SUR) and event-free survival probability (EFS) according to Kaplan-Meier was significantly better for children with positive SR scintigraphy than for the children with a negative SR scan (SUR: 90% vs. 48% at 4 years log rank P < 0.003, EFS: 83% vs. 39% at 4 years, log rank P < 0.0002). CONCLUSIONS: (123)I-mIBG scintigraphy remains the best scintigraphic method for detecting neuroblastoma tumor tissue, whereas additional SR scintigraphy is able to provide significant prognostic information with a minimum of invasiveness.

Comparison of MIBG and pentetreotide scintigraphy in children with neuroblastoma. Is the expression of somatostatin receptors a prognostic factor?

BACKGROUND: Neuroblastoma (NB) is the fourth most common pediatric malignancy and recent reports suggest a prognostic role of somatostatin receptor scintigraphy (SRS) in this disease. MATERIALS AND METHODS: Twenty two patients (pts. mean age 43.9 months) with NB were investigated by 1-123-MIBG and SRS (In-111-pentetreotide). Twenty-seven comparative scans were evaluated and compared for catecholamin excretion, Ultrasound, CT and MRI data. The patients were then divided into three groups. I: patients with manifest disease, II: patients with relapse or minimal disease and III: patients with no evidence of disease. RESULTS: MIBG and SRS scans were concordant in 85% (12 true positive, 7 true negative, 4 false negative). In 4 pts only the MIBG scan was positive. In 9 pts with stage I-III disease or complete remission no relapse was recorded during 19.8 months. In 4 out of 5 pts who died SRS failed to localize the tumor sites but three MIBG scans were positive. Five out of 6 pts with a relapse free interval of 7.9 months had positive SRS and MIBG scans. CONCLUSIONS: in NB SRS can be applied as a specific imaging modality. However, in some pts SRS failed due to the lack of receptor expression. Somatostatin receptor expression seems to be related with a more favourable clinical outcome.

Somatostatin in neuroblastoma and ganglioneuroma.

Neuroblastoma, a childhood tumour of the sympathetic nervous system, may in some cases differentiate to a benign ganglioneuroma or regress due to apoptosis. Somatostatin may inhibit neuroblastoma growth and induce apoptosis in vitro and was therefore investigated. Using a radioimmunoassay, we found that all ganglioneuromas contained high somatostatin concentrations (> 16 pmol/g), significantly higher than neuroblastomas (n = 117, median 2.8 pmol/g), healthy adrenals, Wilms' tumours, phaeochromocytomas and other neuroendocrine tumours (P < 0.001). Neuroblastomas contained more somatostatin than control tumours (P < 0.001-0.05). Neuroblastomas amplified for the MYCN oncogene contained less somatostatin than non-amplified tumours (1.2 pmol/g versus 4.0 pmol/g, respectively; P = 0.026). In a clinically unfavourable neuroblastoma subset (age > 12 months, stage 3 or 4) 16 children with high concentrations of somatostatin in primary tumours had a better prognosis than 23 with low somatostatin (46.7% versus 0% survival at 5 years, P < 0.005). Scintigraphy using 111In-pentetreotide identified tumours expressing high-affinity somatostatin receptors in vivo. However, no significant correlation was found between somatostatin receptor expression and peptide content in 15 tumours. Similarly, human SH-SY5Y neuroblastoma xenografts grown in nude rats showed low somatostatin concentrations, but were positive for somatostatin receptor scintigraphy. Treatment of these rats with the somatostatin analogue octreotide seemed to upregulate in vivo receptor expression of somatostatin and vasoactive intestinal peptide more effectively than 13-cis retinoic acid. In conclusion, somatostatin in neuroblastoma is associated with differentiation to benign ganglioneuromas in vivo and favourable outcome in advanced tumours. Furthermore, somatostatin receptor scintigraphy may identify tumours with high-affinity receptors in children that might benefit from targeted therapy using synthetic somatostatin analogues.

[Value of 99mTc-MIBI scintigraphy in diagnostic localization of hyperparathyroidism. A prospective study]. / Zum Stellenwert der 99mTc-MIBI-Szintigraphie bei der Lokalisationsdiagnostik des Hyperparathyreoidismus. Eine prospektive Studie.

We evaluated the sensitivity of praeoperative parathyroid imaging using 99mTc-MIBI scintigraphy in planar as well as SPECT technique to detect and localize abnormal parathyroid glands in 36 patients with hyperparathyroidism. Seven out of these patients had been previously operated in the thyroid area. With a sensitivity of 76% (22/29) solid adenomas could be localized correctly. Surgical success was estimated by the weight of the adenomas, by histology and postoperative laboratory findings. Compared to other imaging procedures 99mTc-MIBI-scintigraphy seems to be most sensitive in detecting and localizing abnormal parathyroid glands, especially in previously operated patients. Praeoperative standard in nuclear medicine up to now is Tl-Tc-subtraction scintigraphy, which is technically more difficult, sensitive to artefacts and exposes the patient to more radiation. Based on our experience we would therefore suggest to screen all previously operated patients with 99mTc-MIBI scintigraphy on a routine basis.

Technetium-99m human immunoglobulin (HIG): a new substance for scintigraphic detection of bone and joint infections.

Technetium (99m-Tc)-labelled, polyclonal human immunoglobulin (HIG) has been described as a new agent to detect local infection and inflammation. In this study, we tested 99m-Tc HIG in 55 patients with suspected chronic (n = 42) and acute (n = 13) skeletal infection. Diagnosis was proven operatively (n = 44) and clinically (n = 11), including microbiological culture tests (n = 46). A gamma camera scan was performed 4 and 24 hours after I.v. injection of 500 MBq 99m-Tc-HIG. 99m-Tc-HIG scanning achieved a sensitivity of 91% and a specificity of 93%. We found one false negative and five false positive scintigraphic results in 55 patients. No clinical or biochemical side effects were encountered after 99m-Tc-HIG injection. We recommend this technique especially for localisation of low-grade, chronic osteomyelitis. The mechanisms and kinetics of 99m-Tc-HIG, however, are worth investigating more extensively.

Efficient symptomatic control of carcinoid tumors with somatostatin in patients with disease progression under alpha-interferon therapy.

BACKGROUND/AIMS: We report--as a retrospective observation--on eight patients with malignant carcinoid tumors. MATERIALS AND METHODS: All patients were initially treated with alpha-interferon and received the longacting somatostatin analogue octreotide (SMS 201-995) after disease progression. Tumor growth was monitored by CT-scan or ultrasound. In addition, serum CgA and urinary 5-HIAA values were determined. RESULTS: All patients responded with relief of symptoms within a few days after the start of octreotide therapy. A regression of the tumor size did not occur, however four patients showed no significant progress over a period of nine to more than eighteen months. The endocrine parameter chromogranin A--determined by immunoluminometric assay (ILMA)--was elevated in all eight patients regardless of symptoms and showed a close correlation with the course of disease. The urinary 5-HIAA values were only elevated in seven patients. In addition, 123I-SMS 204-090 scintigraphy could be performed in six patients. Using this method most of the primary tumors and metastases could be detected. CONCLUSIONS: Only octreotide therapy showed a sufficient symptomatic control and has to be considered as progress in drug therapy for patients with malignant carcinoid tumors. In addition, chromogranin A is an interesting endocrine parameter for the follow-up of the secretory activity.

Somatostatin receptor imaging in persistent medullary thyroid carcinoma.

OBJECTIVE: Somatostatin is secreted from thyroid C-cells and seems to play an important part in the regulation of calcitonin secretion. We therefore evaluated the usefulness of somatostatin receptor scintigraphy in the localization of tumour tissue in patients with persistent medullary thyroid carcinoma. DESIGN: A prospective clinical study. PATIENTS: The series consisted of 26 patients with elevated calcitonin levels after total thyroidectomy for histologically proven medullary thyroid carcinoma. METHODS: Somatostatin receptor scintigraphy using 111In-pentetreotide (Octreoscan) was performed in all patients and the results correlated with histology, ultrasonography, computerized tomography, magnetic resonance imaging, plain radiography, bone scintigraphy and selective venous catheterization. Calcitonin and carcinoembryonic antigen levels were measured. RESULTS: The sensitivity of somatostatin receptor scintigraphy for localization of persistent medullary thyroid carcinoma was 57% in patients with histologically proven disease. The results depended on tumour mass (low sensitivity (33%) in minimal residual disease) and on the location of metastases (insensitive in detecting liver metastases). CONCLUSIONS: Somatostatin receptor scintigraphy is of value as an additional diagnostic tool in localizing medullary thyroid carcinoma, especially pulmonary metastases. It is of minor importance in detecting minimal residual disease.