Retrospective web-based multicenter evaluation of ¹8F-FDG-PET and CT derived predictive factors. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan in follicular non Hodgkin's lymphoma.

AIM: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan. PATIENTS, METHODS: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. RESULTS: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10±8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. CONCLUSION: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.

Guidelines on radioiodine therapy for differentiated thyroid carcinoma: impact on clinical practice.

AIM: For the examination of the impact on clinical practice of the guidelines for differentiated thyroid carcinoma (DTC), treatment data from the ongoing Multicenter Study Differentiated Thyroid Carcinoma (MSDS) were analyzed. PATIENTS, METHODS: Patients were randomized to adjuvant external beam radiotherapy (RTx) or no RTx in addition to standard therapy in TNM stages pT4 pN0/1/x M0/x (UICC, 5th ed. 1997). All patients were to receive the same treatment regimen consisting of thyroidectomy, ablative radioiodine therapy (RIT), and a diagnostic 131I whole-body scintigraphy (WBS) 3-4 months after RIT. RESULTS: Of 339 eligible patients enrolled between January 2000 and March 2004, 273 could be analyzed. Guideline recommendations by the German Society for Nuclear Medicine from 1999 and 1992 were complied with within 28% and 82% with regard to the interval between surgery and RIT (4 vs. 4-6 weeks), in 33% and 84% with regard to 131I activity for RIT (1-3 vs. 1-4 GBq; +/- 10%), and in 16% and 60% with regard to 131I activity for WBS (100-300 vs. 100-400 MBq; +/- 10%). CONCLUSIONS: The 1999 guideline revision appears to have had little impact on clinical practice. Further follow-up will reveal if guideline compliance had an effect on outcomes.

[Adjuvant percutaneous radiation of locally advanced papillary and follicular thyroid carcinoma: reflections for the necessity of a prospective multicenter study]. / Adjuvante perkutane Radiatio lokal fortgeschrittener papillärer und follikulärer Schilddrüsenkarzinome: Uberlegungen vor dem Start einer prospektiven Multizenterstudie.

Adjuvant external radiation therapy in patients with locally advanced differentiated thyroid cancer was repeatedly controversially discussed. Results of various retrospective analyzes were contradictory and did not lead to a generally accepted consent. Nevertheless, they allow the assumption that at least subgroups of patients in a pT4 stage with no or microscopic residual disease may benefit from adjuvant external beam therapy. This publication is a review of the literature and illustrates the variety of "strategies" practiced in German clinical centers and the necessity of a prospective multicentric clinical trial.

[A new inherited RET proto-oncogene mutation associated with familial medullary thyroid carcinoma and polymorphisms in adjacent regions]. / Novaia nasleduemaia mutatsiia protoonkogena RET, assotsiirovannaia s semeinym medulliarnym rakom shchitovidnoi zhelezy, i polimorfizmy v okruzhaiushchikh oblastiiakh.

A new point mutation, TCG(Ser)-->GCG(Ala) in codon 891, exon 15 of the RET protooncogene was revealed in two patients from a pedigree with familial medullary thyroid carcinoma (FMTC), but not in healthy persons. A linkage analysis with two well-known and two new intragene polymorphisms showed that informative polymorphic markers, the phenotypic expression of the disease, and the mutation are cosegregated in the studied pedigree. Two new polymorphisms, G/A at position-24 of intron 14 and C/T in codon 836 of exon 14, were found in the RET protooncogene. The frequencies of allele 1 of the polymorphic site in codon 836 were the same (0.96) in the Russian and German populations. This was also characteristic of two polymorphisms revealed earlier, namely, the sites in codons 691 (0.80 and 0.81, respectively) and 904 (0.21 and 0.22). However, the frequency of allele 1 of the polymorphisms in intron 14 differed significantly (0.87 and 0.77, respectively).

Progressive heterogeneity of myocardial perfusion in heart transplant recipients detected by thallium-201 myocardial SPECT.

UNLABELLED: Progressive graft atherosclerosis is a serious complication in long-term survivors after heart transplantation. Coronary angiography is insensitive with regard to the early and characteristic alterations. We evaluated the progression of these abnormalities and the influence of former rejection episodes. METHODS: Early after transplantation, 43 patients (34 men, mean age 53.7 +/- 10.7 yr) underwent stress and redistribution 201Tl myocardial SPECT after treadmill exercise. Twenty patients were followed-up to the second postoperative year, and 13 patients to the third postoperative year. Thallium-201 distribution and kinetic abnormalities were documented in a scheme enclosing 20 myocardial segments. Additionally, a score was developed that measured the degree of inhomogeneity of 201Tl distribution and the severity of perfusion defects, respectively. RESULTS: Regarding scintigraphy, pathologic results could be found in 40% of segments (redistribution, 25%; reverse redistribution, 30%; persistent defects, 49%). Score values in heart transplant recipients differed significantly from normal controls (p < 0.001) and were comparable to patients with single vessel disease of their native hearts. Thallium-201 inhomogeneity in recipients after treatable rejection episodes did not differ from results in recipients without any biopsy-proven rejection. The follow-up of cardiac transplant patients revealed a significant increase of score values up to the third year after transplantation (p < 0.02), despite reproducible normal angiography. There was no direct correlation between score values and IVUS results, although there was a parallel trend in 10 of 12 follow-ups. CONCLUSION: Despite normal coronary angiography, 201Tl myocardial SPECT frequently revealed pathologic results in heart transplant recipients. Scintigraphic results did not correlate with intimal thickening of epicardial coronary arteries accessible to intravascular ultrasonography in the early phase after transplantation. The presented score of inhomogeneity might reveal progressive disease possibly caused by small vessel alterations.

[Conventional nuclear medical diagnosis in the after care of heart transplantation]. / Konventionelle nuklearmedizinische Diagnostik in der Nachsorge nach Herztransplantation.

Actually more than 80% of heart recipients survive the first postoperative year. Early death is mainly caused by rejection and acute infection. After the first year progressive graft atherosclerosis has the greatest impact on prognosis. The review presents scintigraphic methods that have reached clinical impact in the diagnosis of rejection and vascular complications. Immunoscintigraphy with 111In-labelled monoclonal antibodies against myosin proved to be of importance in the diagnosis of rejection especially in long-term follow-up. Perfusion scintigraphy reveals vital and ischemic myocardium. In heart transplant recipients radionuclide ventriculography has been widely replaced by echocardiography. Up to now, the evaluation of increasing nerval integration with 123I-MIBG has not reached clinical impact.

Reduced GABAA receptor density contralateral to a potentially epileptogenic MRI abnormality in a patient with complex partial seizures.

Imaging cerebral GABAA receptor density (GRD) with single-photon emission tomography (SPET) and iodine-123 iomazenil is highly accurate in lateralizing epileptogenic foci in patients with complex partial seizures of temporal origin. Limited knowledge exists on how iomazenil SPET compares with magnetic resonance imaging (MRI) in this regard. We present a patient with complex partial seizures in whom MRI had identified an arachnoid cyst anterior to the tip of the left temporal lobe. Contralaterally to this structural abnormality, interictal electroencephalography (EEG) performed after sleep deprivation disclosed an intermittent frontotemporal dysrhythmic focus with slow and sharp waves. On iomazenil SPET images GRD was significantly reduced in the right temporal lobe and thus contralaterally to the MRI abnormality, but ipsilaterally to the pathological EEG findings. These data suggest that iomazenil SPET may significantly contribute to the presurgical evaluation of epileptic patients even when MRI identifies potentially epileptogenic structural lesions.

New renal function imaging agents. I. Synthesis and biological characterization of a [99mTc]diaminomercapto(thio)ether (DAMTE).

The present study describes the synthesis of a [99mTc]diaminomercapto(thio)ether (DAMTE-derivative) as a first compound of a new class of 99mTc-complexes which is tubular excreted. 10-Benzoyl-8-keto-7-aza-2-amino-4,10-dithia-decanoic acid (CO2-DAMTE 3) was synthesized by the reaction of succinimidyl-S-benzoyl-thioglycolate and (S)-2-aminoethyl-L-cysteine. The respective technetium complex, 99mTc-CO2-DAMTE was obtained in radiochemical yields of about 70% using stannous chloride as reducing agent. Hydrolysis of the protecting group was performed either prior to the complexation of pertechnetate ("cold kit") or during the labelling reaction ("hot kit"). Organ distribution was determined in Wistar rats. Within 24 h 40% of the activity were excreted into the feces and 43% into the urine, whereas 10% were retained in the kidneys. In contrast, a first human study showed a very fast renal elimination of 99mTc-CO2-DAMTE, a low liver uptake (< 10%) and no retention in the kidneys. The renal clearance of approx. 240 mL/min/1.73 m2 in addition to the protein binding of > 95% suggests an effective tubular excretion of the compound.

Scintigraphic detection of osteomyelitis in osteopetrosis.

METHODS AND RESULTS: The diagnosis of osteomyelitis in severe osteopetrosis may be difficult since altered bone architecture and fractures veil the typical radiographic signs of inflammation. We present a case of adult osteopetrosis with questionable clinical and radiographic signs of two osteomyelitic foci in the foot. CONCLUSION: Despite severe skeletal disease, the combination of skeletal and leukocyte scintigraphy suggested the diagnosis of infection.

White blood cell scintigraphy with monoclonal antibodies in the study of the infected endoprosthesis.

Forty-three patients with suspected infection of a hip or a knee prosthesis were studied with white blood cell scintigraphy (WBC), using technetium-99m (n = 37) or iodine-123 (n = 6) labelled monoclonal mouse antibody (MoAb). Previously, all patients had undergone skeletal scintigraphy, which was performed as a three-phase study in 33 cases. The final diagnosis was established by open surgery, histology and culture in 37 cases, by puncture and culture in 3 cases, and by clinical follow-up of at least 6 months in 3 cases. Eighteen prostheses were infected, 25 uninfected. The delayed phase of skeletal scintigraphy had a sensitivity of 92%, a specificity of 24% and an accuracy of 48% in the detection of infection. The perfusion and blood pool activity of the three-phase bone scan had a sensitivity of 67%, a specificity of 71% and an accuracy of 70%. The diagnostic value of WBC was sensitivity 89%, specificity 84% and accuracy 86%. WBC with 99m-Tc-MoAb is easy to perform and always available. Its diagnostic accuracy is similar to conventional WBC scintigraphy with either indium-111 or technetium-99m.