Search

Previous findings of our group showed the chemokine receptor CXCR4 as a suitable target in PET/CT-imaging of axial bone infections, early postoperative osteomyelitis and periprosthetic infections. The aim of this study was to verify specific uptake of 68 Ga-Pentixafor in chronic osteomyelitis., Methods: 29 consecutive patients who underwent 68 Ga-Pentixafor-PET/CT with clinically suspected osteomyelitis were evaluated retrospectively. Bone tissues of 6 patients were available and evaluated by immunohistochemical staining for CXCR4 and autoradiography with 68 Ga-Pentixafor. Staining was performed with an anti-CXCR4 antibody. In order to detect lymphocytic infiltration and CXCR4-expressing lymphocytes double immunofluorescence with an anti-CD3 and anti-CXCR4 antibody was performed., Results: 68 Ga-Pentixafor-PET/ CT was true positive in 16 and true negative in 13 patients. In available bone tissue samples, immunohistochemical staining of CXCR4 expression and autoradiography with 68 Ga-Pentixafor was highly positive. Double immunofluorescence was able to detect CXCR4-expressing T-lymphocytes within all bone samples while a control sample of noninfected tibial bone was negative for CXCR4., Conclusion: 68 Ga-Pentixafor-PET/CT specifically shows CXCR4-expressing immune cells in chronic osteomyelitis and is therefore a suitable method for imaging chronic infection of the skeleton.Der Chemokinrezeptor CXCR4 konnte in einer Pilotstudie unserer Arbeitsgruppe als geeignete Zielstruktur zur PET/CT-Bildgebung von frühen postoperativen und periprothetischen Osteomyelitiden sowie Osteomyelitiden im Stammskelett identifiziert werden. In dieser Studie haben wir untersucht, ob 68 Ga-Pentixafor spezifisch CXCR4-exprimierende Entzündungszellen in einer chronischen Osteomyelitis darstellen kann., Methoden: Es erfolgte eine retrospektive Auswertung von 29 Patienten mit klinischem Verdacht einer chronischen Osteomyelitis, die mittels 68 Ga-Pentixafor-PET/CT untersucht wurden. Hiervon lagen uns in 6 Fällen Knochengewebe zur immunhistochemischen und autoradiographischen Evaluation vor. Die Immunhistochemie wurde mit einem anti-CXCR4 Antikörper durchgeführt. Des Weiteren wurden ein anti-CD3 und der anti-CXCR4-Antikörper zur Detektion CXCR4-exprimierender Lymphozyten am Ort der Entzündung mittels Doppel- Immunfluoreszenz verwendet., Ergebnisse: Die 68 Ga-Pentixafor-PET/CT war bei 16 Patienten richtig positiv und bei 13 Patienten richtig negativ. Die Färbungen der verfügbaren Knochenpräparate waren sowohl in der Immunhistochemie als auch in der Autoradiographie deutlich positiv. In der Immunfluoreszenz konnten zudem CXCR4-exprimierende Lymphozyten am Ort der Entzündung in allen Proben nachgewiesen werden. Die Kontrolle eines Präparats einer nicht infizierten distalen Tibia zeigte dagegen keine CXCR4-oder CD3-Expression., Fazit: Mit der 68 Ga-Pentixafor-PET/CT können spezifisch CXCR4-exprimierende Lymphozyten am Ort der Entzündung nachgewiesen werden. Die 68 Ga-Pentixafor-PET/CT stellt eine geeignete Methode in der Diagnostik chronischer Osteomyeltiden dar., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

The diagnostic strategy in patients with fever or inflammation of unknown origin remains a major clinical challenge. The aim of this study was to evaluate the role of 18 F-FDG-PET/CT in patients with unexplained elevated C-reactive protein with or without fever. Contribution of 18 F-FDG-PET/CT to the final diagnosis was evaluated. In addition we determined whether a differentiation between patients with or without fever is clinically reasonable., Patients, Methods: We retrospectively analysed 72 consecutive patients with unexplained elevated C-reactive protein levels (above 8mg/l) that underwent 18 F-FDG-PET/CT in our facility between 10/2009 and 11/2012. 18 F-FDG-PET/CT was considered a so-called diagnostic scan when results decisively led to a final diagnosis and adequate therapy with a response of symptoms was initiated due to the PET/CT result., Results: In 60/72 patients (83%) a final diagnosis was established. Diagnoses included infections (58%), non-infectious inflammatory diseases (29%) and malignancies (8%). 18 F-FDG-PET/CT was true positive in 47 cases (65%) and the diagnostic scan in 29 patients (40%). Sensitivity of 18 F-FDG-PET/CT was 81% and specificity was 86%. Diagnostics, final diagnoses, 18 F-FDG-PET/CT results, SUVmax, C-reactive protein levels and the diagnostic scan did not differ significantly between patients with fever and patients without fever., Conclusion: 18 F-FDG-PET/CT is a useful method in the diagnostic workup of patients with inflammation of unknown origin. In our series there was no significant difference between patients with or without fever. Regarding 18 F-FDG-PET/CT-imaging inflammation of unknown origin and unexplained fever can be joined to one entity.

Objective: Primary risk factors in patients with differentiated thyroid carcinoma (DTC) are well established. In our institution, secondary risk stratification has been performed with stimulated Thyroglobulin (sTg; TSH > 30 mIU/l) within six months after primary therapy since 2001. In this study, we evaluated the predictive value of sTg for long-term disease-free survival (DFS)., Patients, Methods: Data of 202 consecutive patients with DTC were analyzed retrospectively. Median follow-up time was 6.4 years (12 months to 16.2 years). Patients were staged according to Union International Contre le Cancer (UICC) criteria. Primary risk stratification was carried out according to European Thyroid Association criteria. Initially, 134 patients (66%) were classified as low-risk and 68 patients (34%) as high-risk. The influence of established risk factors and sTg on DFS was analyzed at three different time points, up to 36 months after initial therapy., Results: In total, 169 (84%) of all patients remained in complete remission after surgery followed by radioiodine-therapy. Six patients (3%) developed tumour recurrence after initial complete remission. Primary risk factors for persistent disease were male sex, follicular or oncocytic tumour, primary tumour > 4 cm in diameter, initial lymph node involvement, initial metastatic disease and microscopic or macroscopic residual tumor. sTg ≤ 0.3 ng/ml measured within six months after initial therapy was a highly significant predictor (p ≤ 0.001) for lasting DFS, 99% of patients with sTg ≤ 0.3 ng/ml were in complete remission 36 months after initial therapy., Conclusions: A stimulated Tg ≤ 0.3 ng/ml within six months after initial therapy is a reliable predictor for long-term disease-free survival independent of primary risk stratification.

The AMG implies far-reaching implications for the synthesis of new radiopharmaceuticals for clinical trials., Aim, Methods: As a part of the DFG-funded Clinical Research Group (KFO 179) a project designated "Immuno-PET for assessment of early response to radiochemotherapy of advanced rectal cancer" was initiated. This trial is focused on a trivalent bispecific humanized monoclonal antibody, and a 68Ga-labeled peptide. Following the new regulatory framework we established a GMP-compliant cleanroom laboratory and applied for a manufacturing permission., Results: During the project constructural, personnel and organizational conditions for a successful application were established, including a quality management system. A GMP-conform cleanroom laboratory class C was constructed, equipped with a two-chamber lock. The actual manufacturing is performed in a closed system with subsequent sterile filtration. The manufacturing processes have been automatised and validated as well as the necessary quality controls. The manufacturing permission was granted after an official inspection., Conclusions: The new German Drug Act is considered as a break in the production practice of nuclear medicine. The early involvement and communication with the authorities avoids time-consuming and costly planning errors. It is much to be hoped that the new legal situation in Germany will not cause serious impairments in the realization of clinical trials in German nuclear medicine.

Unlabelled: The prevalence of cervical lymphadenopathy in autoimmune thyroiditis (AIT) patients is actually unknown. The aim of the study was the detailed retrospective evaluation of 6 index-patients with lymphadenopathy in Robbins level VI and a prospective study with high resolution ultrasound of lymphadenopathy in AIT patients compared with controls in all compartments of the neck, accessible to sonographic evaluation., Patients, Methods: The retrospective study comprises six patients with AIT, evaluated for enlarged Robbins level VI-LN. We report the findings of fine-needle aspiration Cytology, clonal analysis, histology, and serological testing. The prospective study evaluated the prevalence of lymphadenopathy in 49 consecutive patients with AIT (group 1) and 49 consecutive patients with normal thyroids or nontoxic goiter (group 2)., Results: In the retrospective study, cytology of paratracheal LN revealed reactive lymphoid hyperplasia in 5/6 of the cases and a centroblastic lymphoma in one patient. The presence of monoclonal lymphatic cells was excluded in 5/6 patients and proven in 1/6 patients. Actual viral-infections were ruled out. In the prospective study AIT-patients showed significantly more enlarged LN in Robbins level II-IV and VI compared to controls. We found no correlation between lymphadenopathy, age, thyroid volume and nodularity, or autoantibody levels. During follow-up in 34 group 1-patients, lymphadenopathy remained stable in 28 patients, and decreased in 6 patients., Conclusion: Lymphadenopathy in Robbins level II-IV and VI is common in AIT-patients and most probably related to the autoimmune process.

Aim: of this study was to validate a newly developed high energy probe (positron emission probe, PEP) optimised for localising PET tracers in vivo., Patients and Methods: Physical investigations included determination of full width at half maximum (FWHM) values at a distance of 1 cm and angular resolution using different point sources. Values obtained with the new probe were compared to those of a conventional gamma probe (CGP). Additionally, PET studies were performed in 36 patients (6 women, 30 men) with proven head and neck cancer and suspected lymph node metastases (Axis, Marconi/Philips) after administering 250-320 MBq (18)F-FDG. Subsequent to PET investigations (18)F-FDG uptake in cervical regions was measured using the PEP. PEP investigations were carried out bilaterally in 5 lymph node (LN) levels (Robbins' classification of the neck). Results of probe studies were correlated with visual and semiquantitative PET evaluations, US and histological findings., Results: FWHM of the new probe was 7 mm (CGP 22 mm) at 662 keV ((137)Cs) and angular resolution resulted in 8 degrees (CGP 60 degrees ). In 29 out of 36 patients LN metastases were suspected due to ultrasound investigations. After neck dissection, histology confirmed LN metastases in 21 patients. Sensitivity (sens.) of US amounted to 95% and specificity to 40%. In 18/21 patients LN metastases were detected by PET (sens. 86%). PET scans failed to diagnose the LN status correctly in 6/36 patients (accuracy 83%). Employing the PEP probe in 20/21 patients LN metastases were identified (sens. 95%), and LN status was determined accurately in 29/36 patients (accuracy 81%). Tumour/background ratios of PEP measurement and results of semiquantitative PET analyses were comparable., Conclusions: PEP measurement is a promising method for preoperative planning of the extent of neck dissection in patients with head and neck cancer and further for radioguided localising PET tracer accumulation during surgery.

Aim: The extent of urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated correlations between UIE and radioiodine uptake (RIU) as well as effects of radioiodine therapy on UIE in patients with autonomous goitre., Patients, Methods: In 197 consecutive patients with thyroid autonomy, UIE was measured twice during radioiodine test (RITe) and correlated with RIU. In 98 of these patients, thyroglobulin and thyroid volume (V) were determined prior to therapy. Individual changes in urinary iodine excretion (DeltaUIE) and TG (DeltaTG) could be investigated four weeks (4W) and six months (6M) after radioiodine therapy. Additionally, DeltaV was determined 6M after therapy. DeltaUIE, DeltaTG and DeltaV were correlated with target dose and target volume., Results: Patients with higher iodine excretion exhibited significantly lower thyroidal radioiodine uptake values. Twofold increased UIE prior to therapy decreased radioiodine uptake by 25%. Compared with pretherapeutic values, UIE and TG were significantly increased four weeks after radioiodine therapy (p < 0.001). Median values of both parameters were found to be doubled. The product of target dose and target volume was not only correlated with a decrease of thyroid volume 6M after therapy, but also with an increase of UIE and TG in the early phase after therapy., Conclusions: It was confirmed that UIE during RITe is a measure for iodine intake and can be used to investigate the competition between stable iodine and radioiodine. The increase of UIE and TG four weeks after therapeutic administration of radioiodine can be explained by disintegrated thyroid follicles. The therapy-induced iodine release may be one important cause for the development of hyperthyroidism in some patients during the first weeks after radioiodine therapy. It may contribute to the known decrease of radioiodine uptake after preapplications of 131I in various thyroid diseases.

Aim: Urinary iodine excretion (UIE) provides information about iodine supply and release. In the present study we investigated effects of the application of different radioiodine isotopes on UIE in patients with differentiated thyroid carcinoma (DTC)., Patients, Methods: In 91 consecutive patients with DTC UIE, measured as iodine/creatinine ratio, was determined before and after application of 123I and 131I for diagnostic or therapeutic purposes. Additionally, remnant volume (V) was determined prior to therapy. Group A consisted of 33 patients with supposed successful ablation of DTC. These patients received 370 MBq 131I for diagnostic use and served as controls. 58 patients (group B) with remnants, relapses and metastases received 370 MBq 123I for diagnostics prior to therapy with 1.5-22.2 GBq 131I. Factors influencing individual changes in urinary iodine excretion (deltaUIE) were investigated by using non-parametric tests., Results: In group A UIE did not change significantly after application of 131I. As well, UIE remained unchanged after diagnostic application of 123I in group B. In contrast, UIE increased significantly already 24 h after therapeutic application of 131I in this group. In patients with small remnants (V < 2.5 ml) a significant but only moderate increase of UIE could be observed (average increase: 47 microg I/g crea). In patients with larger remnants, with relapses or metastases increase of UIE values was significant and more pronounced., Conclusions: It was confirmed that UIE increased significantly during radioiodine therapy in patients with DTC and radioiodine-accumulating tissue. The increase of UIE after therapeutic administration of radioiodine can be explained by the disintegrated thyroid follicles in thyroid remnants. The radioiodine-induced iodine release may be one reason for thyroid "stunning" even after application of diagnostic amounts of 131I.

Aim: In 214 patients with benign thyroid diseases the time-course of urinary iodine excretion (UIE) was investigated in order to identify changes after radioiodine therapy (RITh)., Method: UIE was measured photometrically (cerium-arsenite method) and related to urinary creatinine on the first and last day of the radioiodine test and then three days, seven days, four weeks, and six months after 131I administration., Results: As compared with the level found immediately before radioiodine therapy, median UIE had almost doubled four weeks after therapy and was still significantly elevated six months after therapy. This increase correlated significantly with the target volume as measured by scintigraphy and sonography., Conclusions: The persistent elevation of UIE for months after RITh is a measure of treatment-induced damage to thyrocytes. Therefore, in view of the unfavourable kinetics of iodine that follow it, RITh should if possible be given via a single-dose regime.