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- Aarnio, Mikko, et al.
(författare)
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Evaluation of PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [11C]D-deprenyl´s usefulness as a marker of acute inflammation.Methods: An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain. Fourteen adult male Sprague-Dawley rats and three tracers [11C]D-deprenyl, [11C]L-dideuterumdeprenyl and [18F]fluorodeoxyglucose were used. Results: No [11C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [11C]D-deprenyl and [11C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [18F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [18F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [11C]D-deprenyl and [11C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.Conclusions: Contrary to our expectations, of the three tracers only [18F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [11C]D-deprenyl and [11C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.
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| 2. |
- Aarnio, Mikko, et al.
(författare)
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Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.
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| 3. |
- Adde, Magdalena, 1960-, et al.
(författare)
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Little usefullness of mid-treatment FDG-PET and biopsy for treatment intensification in patients with aggressive lymphoma
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: To evaluate the experiences of introducing mid-treatment FDG-PET in patients with aggressive lymphoma, in a population based program with decentralized examinations, with emphasis on finding patients who would benefit from dose-escalation. Patients and Methods: Twenty-five patients with aggressive lymphoma were included. Twenty-four (95%) of these having an aggressive B-cell lymphoma (84% diffuse large B-cell lymphoma) were treated with CHOP-like treatment given at two week intervals + rituximab. One patient having an anaplastic T-cell lymphoma was treated with CHOEP-14. Mid-treatment FDG-PET was performed and assessed as positive, uncertain or negative for remaining lymphoma. The intention was to perform a biopsy in those with a positive FDG-PET, and, to change to a platina-containing therapy and consolidate with high-dose therapy if viable lymphoma was found. Retrospective review of the PET investigations was done. Living patients were followed for a median of 22 months. Results: At primary analysis five patients (20%) had positive uptake on FDG-PET. Two of them had biopsy-proven viable tumor but did not complete the planned salvage treatment, one due to chemotherapy toxicity and one due to progressive disease during salvage therapy. Two patients had a negative biopsy and one patient had no biopsy due to technical difficulties at diagnosis. These three patients remain in remission after standard treatment. Out of seven patients (28%) having “uncertain” uptake two relapsed. Thirteen patients (52%) were negative,two of whom relapsed giving a negative predictive value of 85%. Conclusion: Mid-treatment FDG PET-CT in order to find patients with biopsy-proven aggressive lymphoma, who can be salvaged with dose escalation, was not feasible in clinical routine.
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| 7. |
- Leeb, Sarah, 1989-, et al.
(författare)
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The unfolded ß-barrel of SOD1 is in a compact state, stabilised by long-range hydrophobic contacts.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The unfolded state of a globular protein in a physiologically relevant environment is by no means an inert random coil. On the contrary, its structural and dynamic properties are crucial for e.g., protein folding and aggregation. Despite its importance, it has been studied relatively sparsely, which is partly due to its low population which tend to obstruct detailed biophysical characterization. Here, introduction of two destabilizing core mutations allow us to study the unfolded state of the central b-barrel of Superoxide Dismutase 1 under native conditions. In order to structurally characterise the unfolded state, we use high-resolution nuclear magnetic resonance (NMR), including paramagnetic relaxation enhancement, to obtain constraints for the generation of unfolded ensembles. The results show that the unfolded state is more compact than the chemically denatured state of the same protein. This compacted state seems to be stabilised by long-range hydrophobic contacts, out of which many coincide with those found in the native state. We also investigated the previously observed destabilising effect on the unfolded state by a poly-anion, and find that; the interaction does not alter the overall ensemble dimensions, nor the pattern in native-like contacts. On the other hand, addition of the chemical denaturant urea results in a more expanded state. The varying compaction with different co-solutes was validated by pulsed-field gradient NMR diffusion measurements. Unlike helical proteins, b-proteins lack the ability to fulfil hydrogen bonds by local native interactions. This forces specific prerequisites on the collapsed pre-folding state. Here, the compaction is enabled by both native-like and non-native long-range contacts in the unfolded ensemble, and we suggest that the average topology of the collapsed state is determined by the sequence distribution of hydrophobic patches, separated by non-interacting hydrophilic clusters.
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| 8. |
- Regula, Naresh, 1985-, et al.
(författare)
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Comparison of 68Ga-PSMA-11 PET/CT with 18F-fluoride PET/CT for detection of bone metastatic disease in prostate cancer
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- 18F-fluoride positron emission tomography/computed tomography (PET/CT) is considered the most sensitive technique to detect bone metastasis in prostate cancer (PCa). 68Ga-PSMA-11 PET/CT is increasingly used for staging of PCa. This study primarily aimed to compare the diagnostic performance of 18F-fluoride PET/CT and 68Ga-PSMA-11 PET/CT in identifying bone metastasis followed by a comparison of 68Ga-PSMA-11 PET/CT with diagnostic CT in identifying soft tissue lesions as a secondary objective.Methods: Twenty-eight PCa patients with high suspicion of widespread disease following curative treatment were prospectively evaluated. PET/CT examinations using 18F-fluoride and 68Ga-PSMA-11 were performed. All suspicious bone lesions were counted, and the tracer uptake was measured as standardized uptake values (SUV) for both tracers. In patients with multiple findings, ten bone lesions with highest SUVmax were selected from which identical lesions from both scans were considered for direct comparison of SUVmax. PSA at scan was correlated with findings of both scans.Results: Both scans were negative for bone lesions in 7 patients (25%). Of 699 lesions consistent with skeletal metastasis in 21 patients on 18F-fluoride PET/CT, 68Ga-PSMA-11 PET/CT identified 579 lesions (83%). In 69 identical bone lesions 18F-fluoride PET/CT showed significantly higher uptake (mean SUVmax:73.1±36.8) compared to 68Ga-PSMA-11 PET/CT (34.5±31.4; p<0.001). PSA at scan was correlated with SUVmax of PSMA-PET (r=58; p=0.01). No correlation was seen between PSA and 18F-fluoride PET/CT measurements. Compared to diagnostic CT, 68Ga-PSMA-11 PET/CT showed better diagnostic performance in locating local (96% vs 61%, p=0.004) and lymph node (94% vs 46%, p<0.001) metastasis.Conclusion: 68Ga-PSMA-11 PET/CT was able to detect majority of bone lesions that were positive on 18F-fluoride PET/CT and was better correlated with PSA at time of scan. Further, this study indicates better diagnostic performance of 68Ga-PSMA-11 PET/CT to locate soft tissue lesions compared to diagnostic CT.
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