Hans J. Biersack

Fluorine-18 fluorodeoxyglucose PET in infectious bone diseases: results of histologically confirmed cases.

Abstract.The aim of this study was to evaluate the clinical use of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in acute and chronic osteomyelitis and inflammatory spondylitis. The study population comprised 21 patients suspected of having acute or chronic osteomyelitis or inflammatory spondylitis. Fifteen of these patients subsequently underwent surgery. FDG-PET results were correlated with histopathological findings. The remaining six patients, who underwent conservative therapy, were excluded from any further evaluation due to the lack of histopathological data. The histopathological findings revealed osteomyelitis or inflammatory spondylitis in all 15 patients: seven patients had acute osteomyelitis and eight patients had chronic osteomyelitis or inflammatory spondylitis. FDG-PET yielded 15 true-positive results. The tracer uptake correlated with the histopathological findings in each case. Bone scintigraphy performed in 11 patients yielded ten true-positive results and one false-negative result. Follow-up carried out on two patients revealed normal or clearly reduced tracer uptake, which correlated with a normalisation of clinical data. In early postoperative follow-up it was impossible to differentiate between postsurgical reactive changes and further infection using FDG-PET. It is concluded that acute and chronic osteomyelitis of the peripheral as well as the central skeleton can be detected using FDG-PET. Osteomyelitis can be differentiated from soft tissue infection surrounding the bone. Unlike computed tomography and magnetic resonance imaging, FDG-PET is not affected by metal implants used for fixing fractures. FDG-PET demonstrated promising initial results with respect to treatment monitoring. Nevertheless, in the early postoperative phase FDG-PET seems to be of limited value owing to unspecific tracer uptake.

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment

Objective: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. Method: [18F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. Results: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. Conclusion: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Testicular function after radioiodine therapy for thyroid carcinoma

Abstract.Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23–73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n=25) and 3 months (n=11), 6 months (n=18), 12 months (n=22), and 18 months (n=18) after radioiodine therapy [radioiodine dose (mean ± SEM): 9.8±0.89 GBq]. Before therapy, FSH was 5.4±0.77 IU/l; it increased significantly (P<0.001) to 21.3±2.4 IU/l after 6 months and fell to 7.4±1.3 IU/l after 18 months (normal range: 1.8– 9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178±25.3 pg/ml before therapy to 22.2±5.5 pg/ml after 3 and 29.4±5.7 pg/ml after 6 months and rose to 154±23.3 pg/ml after 18 months (normal range 75– 350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6–9.2 IU/l and 10.4–34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8±0.33 IU/l before therapy to 5.9±0.69 IU/l 6 months after therapy and then fell slowly to 4.0±0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8±0.99 nmol/l at baseline to 19.8±1.7 nmol/l after 12 months and 19.6±1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3–17.9 nmol/IU) fell from 5.8±0.66 nmol/IU to 3.0±0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4±0.49 nmol/IU) and then rose to 5.5± 0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered.

Fluorine-18 fluorodeoxyglucose positron emission tomography findings in spondylodiscitis: preliminary results

Abstract. Nuclear medicine procedures can be helpful in diagnosing spine infections. The purpose of the study was to evaluate the findings of positron emission tomography with fluorine-18 fluorodeoxyglucose (FGD-PET) in the detection of spondylodiscitis. We performed FDG-PET in 16 patients with suspected spondylodiscitis. All the patients were operated and underwent histopathological examination. The FDG-PET findings were graded and evaluated by two independent nuclear medicine physicians. Of the 16 patients, 12 had a histopathologically confirmed spondylodiscitis. In all these 12 patients, FDG-PET was true-positive. In the four patients without spondylodiscitis, FDG-PET showed three true-negative and one false-positive result. In spondylodiscitis, the mean standard uptake value (SUV) of FDG was 7.5 (SD±3.8). The PET scans depicted the paravertebral soft tissue involvement in cases of spondylodiscitis. Our first results showed that FDG-PET is a very sensitive imaging procedure in the detection of spondylodiscitis. Compared to other nuclear medicine procedures, PET enables a rapid imaging with acceptable radiation dose and high spatial resolution.

FDG-PET findings of vertebral compression fractures in osteoporosis: preliminary results.

Abstract: The aim of this study was to evaluate FDG-PET findings in patients with osteoporosis or preclinical osteoporosis and acute vertebral compression fractures in order to determine whether FDG-PET has a value for distinction of pathological from osteoporotic vertebral fractures. 17 patients with a spontaneous compression fracture of the spine were evaluated by bone scanning with Tc-99m HDP, positron emission tomography with fluorine-18 deoxyglucose (FDG-PET) and magnetic resonance imaging (MRI). Osteoporosis had been established in all cases by X-ray and osteodensitometry. PET and bone scan images were scored independently from 0 (no pathological uptake) to 4 (definitive pathological uptake) by two blinded nuclear medicine physicians. The results of the blinded scoring were compared to MRI findings which served as gold standard. In 13 out of 17 patients, MRI demonstrated a vertebral fracture generating from osteoporosis. In 12 of these 13 cases, PET scans were scored with 0 or 1 and categorized as true negative. Standard uptake values (SUV) ranged between 1.1 and 2.4. In one of the 13 patients, PET was interpreted false positive with an uptake score of 3 (SUV = 2.9). Of the 17 patients, MRI revealed a pathological fracture caused by spondylodiscitis in three patients and by plasmacytoma in one patient. In these patients, all PET scans were highly positive with a score of 3 and 4 and SUV values between 3.8 to 9.8. The bone scans of all 17 patients were positive with scores of 3 or 4 but a differentiation between osteoporotic and pathological fractures was not possible. Our preliminary results indicate that acute vertebral fractures that originated from osteoporosis or preclinical osteoporosis tend to have no pathologically increased FDG uptake. Since a high FDG uptake is characteristic for malignant and inflammatory processes, use of FDG-PET may have potential value for differentiation between osteoporotic and pathological vertebral fractures.

Reactor-produced radioisotopes from ORNL for bone pain palliation

The treatment of painful skeletal metastases is a common clinical problem, and the use of therapeutic radionuclides which localize at metastatic sites has been found to be an effective method for treatment of pain, especially for multiple sites for which the use of external beam irradiation is impractical. There are currently several metastatic-targeted agents radiolabeled with various therapeutic radionuclides which are in various stages of clinical investigation. Since neutron-rich radionuclides are produced in research reactors and often decay by emission of beta- particles, most radionuclides used for bone pain palliation are reactor-produced. Key examples of radionuclides produced by single neutron capture of enriched targets include rhenium-186 and samarium-153. In addition, generator systems are also of interest which provide therapeutic daughter radionuclides from the decay of reactor-produced parent radionuclides. One important example is rhenium-188, available from generators via decay of reactor-produced tungsten-188. Tin-117m is an example of a reactor-produced radionuclide which decays with the emission of low-energy conversion electrons rather than by beta- decay. Each of these agents and/or radionuclides has specific advantages and disadvantages, however, the ideal agent for bone pain palliation has not yet been identified. The goal of this paper is to briefly review the production and use of several reactor-produced radionuclides for bone pain palliation, and to discuss the role of the ORNL High Flux Isotope Reactor (HFIR) for the production of many of these radionuclides.

Regional cerebral blood flow single-photon emission tomography with 99mTc-HMPAO and the acetazolamide test in the evaluation of vascular and Alzheimer's dementia

Abstract. The diagnostic potential of technetium-99m hexamethylpropylene amine oxime (HMPAO) following systemic administration of the cerebral vasodilator acetazolamide (acetazolamide test) was evaluated by regional cerebral blood flow (rCBF) single-photon emission tomography (SPET) in patients with Alzheimer’s disease (AD) or vascular dementia (VD). An initial, high-resolution SPET study was performed with 99mTc-HMPAO, and after 2 days the patients were re-evaluated with 99mTc-HMPAO following systemic administration of acetazolamide. Reconstructed SPET slices were evaluated visually and semiquantitatively by a semi-automatic rCBF map method. When 99mTc-HMPAO alone was used, bilateral hypoperfusion was found in the temporal and/or parietal regions in 33% (6/18) of the VD patients and in 70% (23/33) of the AD patients. The corresponding data obtained by quantitative evaluation were 41% (7/17) and 71% (15/21), respectively. The vascular reserve capacity, as determined with the acetazolamide test, was preserved visually in 22% (4/18) and quantitatively in 29% (5/17) of the VD patients, but in 73% (24/33) and 76% (16/21) of the AD patients. The differences in the perfusion patterns between the VD and AD patients were statistically significant (P<0.01, Fischer’s exact test). Of the VD patients with hypoperfusion (bilateral temporal and/or parietal), 4/6 (67%, visual evaluation) and 4/7 (57%, quantitative evaluation) had a decreased vascular reserve capacity as determined with the acetazolamide test. In the AD group of patients the corresponding results were 3/23 (13%) and 4/15 (27%). It is concluded that the acetazolamide test is promising in rCBF SPET to differentiate VD from AD.

18FDG PET and acetazolamide-enhanced99mTc-HMPAO SPET in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), brain and kidney are the most frequently affected organs. Measurements of cerebral blood flow and metabolism by means of positron emission tomography (PET) and single-photon emission tomography (SPET) can contribute to the diagnostic assessment of the involvement of the central nervous system (CNS) in SLE. Functional imaging has been proven to be more sensitive than morphological imaging (magnetic resonance imaging and computed tomography). In this report, we present the case of a 70-year-old female patient, suffering from SLE without symptoms of CNS involvement. In addition to a SPET study using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) and a PET scan with fluorine-18 deoxyglucose (18FDG), a SPET study after acetazolamide injection was performed in order to assess the cerebral perfusion reserve. While the PET scan showed no major abnormalities, and the baseline SPET study revealed only minor changes, the acetazolamide-enhanced SPET study revealed a marked reduction of the cortical perfusion reserve, particularly in both frontal lobes. It is concluded that “preclinical” CNS involvement, mainly caused by pathological mechanisms involving the cerebral blood vessels, can be considered to exist in this patient with SLE.

Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up

BACKGROUND Monocentric and retrospective studies indicate effectiveness of peptide receptor radionuclide therapy targeting somatostatin receptors of neuroendocrine neoplasms. We assessed overall and progression-free survival and adverse events of peptide receptor radionuclide therapy by a multi-institutional, board certified registry with prospective follow-up in five centres in Germany. METHODS A total of 450 patients were included and followed for a mean of 24.4 months. Most patients had progressive low- or intermediate grade neuroendocrine neoplasms and 73% were pretreated with at least one therapy. Primary neuroendocrine neoplasms were mainly derived of pancreas (38%), small bowel (30%), unknown primary (19%) or bronchial system (4%). Patients were treated with Lutetium-177 in 54%, with Yttrium-90 in 17% and with both radionuclides in 29%. Overall and progression-free survival was determined with Kaplan-Meier curves and uni-variate log rank test Cox models. FINDINGS Median overall survival of all patients was 59 (95% confidence interval [CI] 49-68.9) months. Overall survival was significantly inferior in the patients treated with Yttrium-90 solely (hazard ratio, 3.22; 95% CI, 1.83-5.64) compared to any peptide receptor radionuclide therapy with Lutetium-177. Grade II (hazard ratio, 2.06; 95% CI, 0.79-5.32) and grade III (hazard ratio, 4.22; 95% CI, 1.41-12.06) neuroendocrine neoplasms had significantly worse overall survival than grade I neuroendocrine neoplasms. Patients with small neuroendocrine neoplasms of small bowel had significantly increased survival (hazard ratio, 0.39; 95% CI, 0.18-0.87) compared to neuroendocrine neoplasms of other locations. Median progression-free survival was 41 (35.9-46.1) months and significantly inferior in patients treated with Yttrium solely (hazard ratio, 2.7; 95% CI, 1.71-4.55). Complete remission was observed in 5.6% of patients, 22.4% had a partial remission, 47.3% were stable and 4% were progressive as best response. Adverse events of bone marrow and kidney function higher than grade III occurred in 0.2-1.5% of patients. INTERPRETATION These results indicate that peptide receptor radionuclide therapy is a highly effective therapy for patients with low to intermediate grade neuroendocrine neoplasms with minor adverse events.

Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumors in Germany: First Results of a Multi-institutional Cancer Registry

Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.