Malte Clausen

18FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin's lymphoma

PURPOSE The value of 18FDG-PET to predict the outcome after therapy in Hodgkins lymphoma was compared to morphologic staging and ESR. PATIENTS AND METHODS A total of 50 concurrent 18FDG-PET and CT studies were performed in 37 patients with Hodgkins lymphoma. ESR was evaluated 32 times after treatment was completed. RESULTS Out of 39 residual masses found by CT 8 relapses could be proven. Out of 11 CT exams with CR 3 relapses occurred. CT turned out to show a sensitivity, specificity, PPV, NPV, and accuracy of 72%, 21%, 21%, 73%, and 32%, with respect to predict disease-free survival (DFS). 18FDG-PET was positive in 22 examinations with 10 recurrences in this group. Out of 28 negative 18FDG-PET 1 relapse developed 3 years later. 18FDG-PET turned out to show promising sensitivity, specificity, PPV, NPV, and accuracy of 91%, 69%, 46%, 96%, 74%, with respect to predict DFS. ESR was elevated in 12 studies of which 5 relapses could be proven, while out of 20 normal ESR-studies 3 relapses occurred. Thus, ESR turned out to show sensitivity, specificity, PPV, NPV, and accuracy of 63%, 71%, 42%, 85%, and 75%, with respect to predict DFS. In summary, only 18FDG-PET was able to predict DFS statistically significant. CONCLUSION 18FDG-PET can be very useful in patients with residual masses after treatment.

Prognostic relevance of FDG PET in patients with neurofibromatosis type-1 and malignant peripheral nerve sheath tumours

PurposeIn patients with neurofibromatosis type-1 (NF1) and malignant peripheral nerve sheath tumours (MPNSTs), survival rates are low and time to death is often less than 2 years. However, there are patients with a more favourable prognosis who develop metastases rather late or not at all. Since histopathology and tumour grading are not well correlated with prognosis, we aimed to evaluate the potential of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) for prediction of patient outcome in MPNST.MethodsFDG PET was performed in 16 patients with NF1 and MPNSTs. Standardised uptake values (SUVs) were calculated for each tumour and correlated to tumour grade and patient outcome in terms of survival or death.ResultsThree patients with tumour grade II had an SUV <3. None of these patients developed metastases or died during a follow-up of 41–62 months. Thirteen patients with tumour grades II and III had an SUV >3. Only one of these patients is still alive after 20 months; the remaining 12 died within 4–33 months. SUV predicted long-term survival with an accuracy of 94%, compared with 69% for tumour grade. In Kaplan-Meier survival analysis, patients with an SUV >3 had a significantly shorter mean survival time, 13 months, than patients with an SUV <3, in whom the mean survival time was 52 months. Tumour grading did not reveal differences in survival time (15 vs 12 months).ConclusionTumour SUV obtained by FDG PET was a significant parameter for prediction of survival in NF1 patients with MPNSTs while histopathological tumour grading did not predict outcome.

Salivary gland protection by amifostine in high-dose radioiodine treatment: results of a double-blind placebo-controlled study.

PURPOSE Salivary gland impairment is a well-recognized side effect following high-dose radioiodine treatment (HD-RIT). Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. Therefore, the effect of amifostine was studied in HD-RIT. PATIENTS AND METHODS Parenchymal function was assessed by quantitative salivary gland scintigraphy performed prospectively in 50 patients with differentiated thyroid cancer before and 3 months after HD-RIT with either 3 GBq iodine ((131)I) (n=21) or 6 GBq (131)I (n=29) in a double-blind, placebo-controlled study. Twenty-five patients were treated with 500 mg/m2 amifostine intravenously before HD-RIT and 25 patients served as controls, who received physiologic saline solution. Xerostomia was graded according to World Health Organization (WHO) criteria. RESULTS Before HD-RIT in 25 control patients, uptake of technetium-99m (99mTc)-pertechnetate was 0.45%+/-0.16% and 0.42%+/-0.16% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function was significantly (P < .001) reduced by 40.2%+/-14.1% and 39.9%+/-15.3% in parotid and submandibular glands, respectively. Nine control patients developed grade I and two grade II xerostomia. In 25 amifostine-treated patients, uptake of 99mTc-pertechnetate was 0.46%+/-0.16% and 0.43%+/-0.17% in parotid and submandibular glands, respectively. Three months after HD-RIT, parenchymal function of salivary glands was not significantly altered (P=.691) and xerostomia did not occur in any of these patients. CONCLUSION Parenchymal damage in salivary glands caused by HD-RIT can significantly be reduced by amifostine, which may improve the quality of life of patients with differentiated thyroid cancer.

Long-term effects of ‘ecstasy’ abuse on the human brain studied by Fdg Pet

The popular recreational drug, ‘ecstasy’, mainly contains 3,4-methylenedioxymethamphetamine (MDMA) as the psychotropic agent. MDMA is suspected of causing neurotoxic lesions to the serotonergic system as demonstrated by animal studies, examinations of human cerebrospinal fluid, and the first positron emission tomography (PET) studies using the serotonin transporter ligand [11C]-McN5652. Damage of serotonergic afferents might mediate long-lasting alterations of cerebral glucose metabolism as a secondary effect. To study a relationship between ecstasy use and long-lasting alterations, PET using 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) was performed in 93 ecstasy users and 27 subjects without any known history of illicit-drug abuse. As an index of glucose metabolism, mean normalized FDG uptake was determined in both groups using a computerized brain atlas, and was compared for a selected number of brain regions. FDG uptake was normalized in each individual by dividing local FDG uptake by the maximum FDG uptake in the individuals brain. Within the group of ecstasy users we examined the relationship between FDG uptake and cumulative ecstasy dose, time since last ecstasy ingestion at the time of PET scanning, and age at first ecstasy use, respectively. Normalized FDG uptake was reduced within the striatum and amygdala of ecstasy users when compared to controls. No statistically significant correlation of the FDG uptake and the cumulative dose of ecstasy was detected. A positive correlation was found in the cingulate between FDG uptake and the time since last ecstasy ingestion. As compared to the control group, normalized FDG uptake in the cingulate was reduced in ecstasy users who took ecstasy during the last 6 months, while it was elevated in former ecstasy users who did not consume ecstasy for more than 1 year. FDG uptake was significantly more affected in ecstasy users who started to consume ecstasy before the age of 18 years. In conclusion, ecstasy abuse causes long-lasting effects on glucose metabolism in the human brain. These effects are more severe in the case of very early abuse. However, several questions still remain to be answered, i.e. the correlation of the neuronal alterations and the history of ecstasy use (cumulative dose, and time since the last dose) and its reversibility.

Quantitative salivary gland scintigraphy in the diagnosis of parenchymal damage after treatment with radioiodine

SummaryThis study was undertaken to quantify salivary gland parenchymal damage after radioiodine treatment with a standard protective regimen of ascorbic acid. Altogether, 106 patients underwent quantitative salivary gland scintigraphy with 99Tcm-pertechnetate prior to and 3 months after radioiodine therapy. Parenchymal function was quantified by calculating 99Tcm-pertechnetate uptake 13 min post-injection. Patients received 131I doses ranging from 400 MBq to 24 GBq (cumulative). Among the patients who received large doses of 131I, severe parenchymal destruction could be visually analysed as well as quantitatively evaluated. In contrast, after low-dose radioiodine treatment, mild parenchymal impairment was demonstrated by quantitative evaluation only. In conclusion, standardized quantitative salivary gland scintigraphy is essential for the reliable detection of mild parenchymal malfunction. Despite the standard protection regimen using ascorbic acid as a sialogogue, radioiodine therapy induces loss of salivary gland parenchymal function even with low doses of 131I.

Salivary gland protection by amifostine in high-dose radioiodine therapy of differentiated thyroid cancer

BackgroundSalivary gland impairment following high-dose radioiodine treatment is a well-recognized side effect, in general caused by free radicals. Therefore, it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy.Patients and MethodQuantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq 1–131. Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectiveley with 9 control patients. Xerostomia was graded according to WHO criteria.ResultsIn 9 control patients high-dose radioiodine treatment significantly (p < 0.01) reduced Tc-99m-pertechnetate uptake by 35.4 ±22.0% and 31.7 ±21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them.ConclusionParenchymal damage in salivary glands induced by high-dose radioiodine treatment can be reduced significantly by amifostine. This may help to increase patients’ quality of life in differentiated thyroid cancer.ZusammenfassungHintergrundEine SchÄdigung der Speicheldrüsen mit konsekutiver Xerostomie ist eine bekannte, durch freie Radikale verursachte Nebenwirkung der hochdosierten Radiojodtherapie bei Patienten mit differenziertem Schilddrüsenkarzinom. Daher wurde der Effekt des RadikalfÄngers Amifostin nach hochdosierter Radiojodtherapie geprüft.Patienten und MethodeIm Rahmen eines Heilversuchs wurde eine limitierte Anzahl von Patienten untersucht. Vor und drei Monate nach Gabe von 6 GBq 1–131 wurde eine quantitative Speicheldrüsenszintigraphie mit 100 bis 120 MBq Tc-99m-Pertechnetat an 17 Patienten mit differenzierten Schilddrüsenkarzinomen durchgeführt. Acht Patienten erhielten vor Radiojodtherapie 500 mg/m2 Amifostin und wurden mit einer historischen Kontrollgruppe aus neun Patienten verglichen. Eine Xerostomie wurde nach WHO-Kriterien beurteilt.ErgebnisseDie Patienten der Kontrollgruppe wiesen sowohl für die Glandulae parotides als auch für die Glandulae submandibulares eine signifikante Verminderung der Tc-99m-Pertechnetat-Aufnahme um 35,4 ±22,0% bzw. 31,7 +21, 1% (Abbildungen 1 und 2, Tabellen 1 und 2) als Zeichen einer ParenchymschÄdigung auf. Bei drei dieser neun Patienten fand sich eine Xerostomie Grad I (WHO). Im Gegensatz dazu konnte bei den mit Amifostin behandelten Patienten keine signifikante Verminderung der Parenchymfunktion festgestellt werden (p = 0,878). Dementsprechend wies keiner dieser Patienten eine Xerostomie auf.SchluΒfolgerungBei Patienten mit differenziertem Schilddrüsenkarzinom kann die durch hochdosierte Radiojodtherapie regelhaft verursachte ParenchymschÄdigung der Speicheldrüsen signifikant vermindert werden. Dies könnte die LebensqualitÄt dieser Patienten wesentlich verbessern.

Somatostatin receptor scintigraphy in the differential diagnosis of meningioma.

The aim of this study was to evaluate somatostatin receptor scintigraphy (SRS) in patients with meningioma proven or suspected on magnetic resonance imaging (MRI). Prior to surgery, 47 patients were investigated up to 24 h following the injection of 200 MBq 111In-octreotide. Tracer uptake was compared with the histological presence of meningioma. Histology revealed 43 meningiomas, 3 neurinomas and 1 ependymoma. A true-positive SRS result was obtained in 36 patients, in 13 of whom a tumour volume of < 10 ml was noted. A false-negative SRS result was obtained in seven patients, all of whom had a tumour volume of < 10 ml. Whereas MRI alone was decisive in 38 of 47 patients, it could only provide a differential diagnosis in the remaining 9 patients. A positive SRS result confirmed meningioma in five of these patients, and a negative SRS result excluded meningioma in the other four. Therefore, cases of SRS-negative meningioma do exist. Nevertheless, significant clinical benefit can be obtained from functional imaging with 111In-octreotide in patients with an inconclusive MRI result, as large meningiomas can be excluded by scintigraphy alone, whereas meningiomas of any size may be confirmed in combination with specific MRI results.

Lymphoscintigraphy in tumors of the head and neck using double tracer technique.

UNLABELLED Knowledge of possible lymphatic drainage may facilitate planning of surgery for patients with head and neck tumors. Therefore, the aim of this study was to present a method of lymphoscintigraphy with special attention to an accurate correlation of lymphatic drainage to anatomic regions. METHODS Lymphoscintigraphy was performed using a double tracer technique before surgery in a total of 75 patients with squamous cell carcinoma of the head and neck. All patients received 100 MBq 99mTc-colloid at three to four peritumoral sites. A perchlorate solution (2 mL) was given orally to block salivary glands and the thyroid gland. Patients received 50 MBq 99mTc-pertechnetate intravenously for body contouring 20 min postinjection. Planar images were obtained over 5 min each, at 30 min and 4 h postinjection from anterior, right lateral and left lateral views with a large-field-of-view gamma camera. Lymphatic drainage was assessed by visual inspection and assigned to six cervical compartments. RESULTS Neither the salivary glands nor the thyroid gland were seen in any of the patients. In 22 of 75 patients (29.3%), the injection site was the only focal tracer uptake seen. In contrast, lymphatic drainage was identified in the remaining 53 patients (70.7%), and lymph nodes could be assigned easily to the six cervical compartments. Of 75 patients, 36 (48%) exhibited ipsilateral lymphatic drainage. In addition, 17 patients (22.7%) with unilateral tumor showed bilateral (n = 12), contralateral (n = 2) or retropharyngeal (n = 3) lymphatic drainage. In 3 of these 17 patients, bilateral lymph node metastases were proven. A subgroup of 12 patients (16%) exhibited N2c nodal status, despite a unilateral localized primary tumor. In 3 of these 12 patients, surgery was extended as a result of scintigraphic findings from unilateral toward bilateral neck dissection, and histology confirmed nodal involvement in these patients. CONCLUSION Lymphoscintigraphy using the double tracer technique allows an accurate correlation of lymphatic drainage to the six cervical compartments. This may provide the basis for a re-evaluation of its impact in treatment planning of patients with head and neck tumors.

Adjusted Scaling of FDG Positron Emission Tomography Images for Statistical Evaluation in Patients With Suspected Alzheimer's Disease

Background and Purpose. Statistical parametric mapping (SPM) gained increasing acceptance for the voxel‐based statistical evaluation of brain positron emission tomography (PET) with the glucose analog 2‐[18F]‐fluoro‐2‐deoxy‐d‐glucose (FDG) in patients with suspected Alzheimers disease (AD). To increase the sensitivity for detection of local changes, individual differences of total brain FDG uptake are usually compensated for by proportional scaling. However, in cases of extensive hypometabolic areas, proportional scaling overestimates scaled uptake. This may cause significant underestimation of the extent of hypometabolic areas by the statistical test. Methods. To detect this problem, the authors tested for hyper metabolism. In patients with no visual evidence of true focal hypermetabolism, significant clusters of hypermetabolism in the presence of extended hypometabolism were interpreted as false‐positive findings, indicating relevant overestimation of scaled uptake. In this case, scaled uptake was reduced step by step until there were no more significant clusters of hypermetabolism. Results. In 22 consecutive patients with suspected AD, proportional scaling resulted in relevant overestimation of scaled uptake in 9 patients. Scaled uptake had to be reduced by 11.1%± 5.3% in these cases to eliminate the artifacts. Adjusted scaling resulted in extension of existing and appearance of new clusters of hypometabolism. Total volume of the additional voxels with significant hypometabolism depended linearly on the extent of the additional scaling and was 202 ± 118 mL on average. Conclusions. Adjusted scaling helps to identify characteristic metabolic patterns in patients with suspected AD. It is expected to increase specificity of FDGPET in this group of patients.

Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model

BACKGROUND Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. METHODS Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99-Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. RESULTS Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417+/-0.373% and 0.421+/-0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99mTc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3+/-5.3% and 53.6+/-17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6+/-3.4% and 6.5+/-4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. CONCLUSION Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer.