Contributions
Abstract: 91
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of Natalizumab (NTZ) therapy in relapsing remitting MS (RRMS) patients. Due to the insidious onset of clinical symptoms, early diagnosis of PML-activity is often challenging. In addition, immune reconstitution inflammatory syndrome (IRIS) after NTZ withdrawal and recurring MS disease activity in the months after diagnosis of PML complicate disease monitoring and treatment decisions. Here, we explored whether [18F]GE-180, a positron-emission tomography (PET) tracer that binds to the translocator protein (TSPO) expressed by activated phagocytes, can be used to monitor PML related inflammatory activity in the CNS.
Goals: The objective of this study was to directly assess inflammatory activity with TSPO-PET in NTZ-related PML in MS patients. We inquired, whether TSPO tracer uptake is increased in PML lesions and can be used to monitor PML activity over time and thus inform treatment decisions.
Methods: Histologic analysis of TSPO expression was performed in tissue samples from PML cases. Six patients with RRMS and a diagnosis of NTZ-related PML as well as 3 non-MS PML patients underwent [18F]GE-180 TSPO-scans in a Siemens Biograph 64 PET/CT. NTZ-related PML-patients were re-scanned in a 6-12 month interval. A dose of 185MBq [18F]GE-180 was applied intravenously. Thereafter, 60-90 minutes summation images were acquired. Images were assessed by visual and quantitative analysis, where SUVRmean and SUVRmax of lesions were measured and normalized to a reference region. 3T MRI was performed concurrently.
Results: In PML lesions, CD68+ cells showed increased levels of TSPO expression. Correspondingly, TSPO tracer uptake in vivo was increased in early symptomatic PML/IRIS with and without contrast enhancing lesions in the concurrent MRI. In PML survivors chronic PML lesions could be differentiated from recurrent MS lesions by morphology and distribution of TSPO-signal.
Conclusion: [18F]GE-180 TSPO PET tracer can be used to measure inflammatory activity in PML lesions. Therefore, TSPO-PET might be a useful tool to monitor NTZ-related PML activity, differentiate fading immune reconstitution and new MS-activity in PML survivors and inform crucial treatment decisions.
Disclosure: C. Mahler: nothing to disclose
M. Schumacher: nothing to disclose
M. Unterrainer: nothing to disclose
L. Vomacka: nothing to disclose
S. Lindner: nothing to disclose
R. Rupprecht: nothing to disclose
N. L. Albert: nothing to disclose
P. Bartenstein: nothing to disclose
T. Kümpfel: nothing to disclose
D. Merkler: nothing to disclose
A. Gass: Dr. Gass has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Novartis, Biogen, Merck Serono, Sanofi-Genzyme, Roche
M. Kerschensteiner: In the past, M. Kerschensteiner has received honoraria for consulting and presentations from Biogen, Genzyme/Sanofi-Aventis, Med-Day Pharmaceuticals, Novartis and TEVA, as well as research supportfrom Biogen and Genzyme/Sanofi-Aventis.
Abstract: 91
Type: Scientific Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: Progressive multifocal leukoencephalopathy (PML) may occur as a severe side effect of Natalizumab (NTZ) therapy in relapsing remitting MS (RRMS) patients. Due to the insidious onset of clinical symptoms, early diagnosis of PML-activity is often challenging. In addition, immune reconstitution inflammatory syndrome (IRIS) after NTZ withdrawal and recurring MS disease activity in the months after diagnosis of PML complicate disease monitoring and treatment decisions. Here, we explored whether [18F]GE-180, a positron-emission tomography (PET) tracer that binds to the translocator protein (TSPO) expressed by activated phagocytes, can be used to monitor PML related inflammatory activity in the CNS.
Goals: The objective of this study was to directly assess inflammatory activity with TSPO-PET in NTZ-related PML in MS patients. We inquired, whether TSPO tracer uptake is increased in PML lesions and can be used to monitor PML activity over time and thus inform treatment decisions.
Methods: Histologic analysis of TSPO expression was performed in tissue samples from PML cases. Six patients with RRMS and a diagnosis of NTZ-related PML as well as 3 non-MS PML patients underwent [18F]GE-180 TSPO-scans in a Siemens Biograph 64 PET/CT. NTZ-related PML-patients were re-scanned in a 6-12 month interval. A dose of 185MBq [18F]GE-180 was applied intravenously. Thereafter, 60-90 minutes summation images were acquired. Images were assessed by visual and quantitative analysis, where SUVRmean and SUVRmax of lesions were measured and normalized to a reference region. 3T MRI was performed concurrently.
Results: In PML lesions, CD68+ cells showed increased levels of TSPO expression. Correspondingly, TSPO tracer uptake in vivo was increased in early symptomatic PML/IRIS with and without contrast enhancing lesions in the concurrent MRI. In PML survivors chronic PML lesions could be differentiated from recurrent MS lesions by morphology and distribution of TSPO-signal.
Conclusion: [18F]GE-180 TSPO PET tracer can be used to measure inflammatory activity in PML lesions. Therefore, TSPO-PET might be a useful tool to monitor NTZ-related PML activity, differentiate fading immune reconstitution and new MS-activity in PML survivors and inform crucial treatment decisions.
Disclosure: C. Mahler: nothing to disclose
M. Schumacher: nothing to disclose
M. Unterrainer: nothing to disclose
L. Vomacka: nothing to disclose
S. Lindner: nothing to disclose
R. Rupprecht: nothing to disclose
N. L. Albert: nothing to disclose
P. Bartenstein: nothing to disclose
T. Kümpfel: nothing to disclose
D. Merkler: nothing to disclose
A. Gass: Dr. Gass has received honoraria for lecturing, travel expenses for attending meetings, and financial support for research from Novartis, Biogen, Merck Serono, Sanofi-Genzyme, Roche
M. Kerschensteiner: In the past, M. Kerschensteiner has received honoraria for consulting and presentations from Biogen, Genzyme/Sanofi-Aventis, Med-Day Pharmaceuticals, Novartis and TEVA, as well as research supportfrom Biogen and Genzyme/Sanofi-Aventis.