Technetium‐99m‐anti‐tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy

Lacerda, Adriano Machado de; Souza, Sérgio Augusto Lopes de; Gutfilen, Bianca; Fonseca, Léa Mirian Barbosa da; Lopes, Flávia Paiva Proença Lobo; Tonomura, Elise; Teixeira, Patrícia de Fátima dos Santos

doi:10.1111/cpf.12548

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…In line with this strategy, others have recommended fluorescent anti-α 4 β 7 integrin to be used during colonoscopy [ 25 ] or 64 Cu-labelled anti-α 4 β 7 integrin for PET imaging of murine colitis [ 26 , 27 ], but no reports are present on 99mTc-labelled anti-α 4 β 7 integrin mAb. On the contrary, there are several reports describing the use of 99m Tc-anti-TNFa mAbs in several diseases such as rheumatoid arthritis [ 28 ] and Graves’ ophthalmopathy [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

et al. 2023

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Imaging using radiolabelled monoclonal antibodies can provide, non-invasively, molecular information which allows for the planning of the best treatment and for monitoring the therapeutic response in cancer, as well as in chronic inflammatory diseases. In the present study, our main goal was to evaluate if a pre-therapy scan with radiolabelled anti-α4β7 integrin or radiolabelled anti-TNFα mAb could predict therapeutic outcome with unlabelled anti-α4β7 integrin or anti-TNFα mAb. To this aim, we developed two radiopharmaceuticals to study the expression of therapeutic targets for inflammatory bowel diseases (IBD), to be used for therapy decision making. Both anti-α4β7 integrin and anti-TNFα mAbs were successfully radiolabelled with technetium-99m with high labelling efficiency and stability. Dextran sulfate sodium (DSS)-induced colitis was used as a model for murine IBD and the bowel uptake of radiolabelled mAbs was evaluated ex vivo and in vivo by planar and SPECT/CT images. These studies allowed us to define best imaging strategy and to validate the specificity of mAb binding in vivo to their targets. Bowel uptake in four different regions was compared to immunohistochemistry (IHC) score (partial and global). Then, to evaluate the biomarker expression prior to therapy administration, in initial IBD, another group of DSS-treated mice was injected with radiolabelled mAb on day 2 of DSS administration (to quantify the presence of the target in the bowel) and then injected with a single therapeutic dose of unlabelled anti-α4β7 integrin or anti-TNFα mAb. Good correlation was demonstrated between bowel uptake of radiolabelled mAb and immunohistochemistry (IHC) score, both in vivo and ex vivo. Mice treated with unlabelled α4β7 integrin and anti-TNFα showed an inverse correlation between the bowel uptake of radiolabelled mAb and the histological score after therapy, proving that only mice with high α4β7 integrin or TNFα expression will benefit of therapy with unlabelled mAb.

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Section: Discussionmentioning

confidence: 99%

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

et al. 2023

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“…( 76 ) discovered orbital gallium-67 scintigraphy as a predictive marker (OR=1.74, P<0.001), that subsequent studies developed various independent predictive nuclide biomarkers. These predictive markers include baseline 99mTc-anti-TNF-α scintigraphy uptake region of interest (ROI)-ratios on SPECT/CT (P=0.036) ( 79 ), as well as the maximum uptake ratio of four EOMs (U max ) obtained by 99mTc-DTPA SPECT/CT (OR=2.08, P=0.001) ( 80 ), which outperformed CAS among patients with CAS≥3 (AUC=0.850 vs 0.780). For response prediction to ORT, Ujhelyi et al.…”

Section: Imaging Biomarkersmentioning

confidence: 99%

Predictive markers for anti-inflammatory treatment response in thyroid eye disease

Zhang,

Fan,

et al. 2023

Front. Endocrinol.

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Anti-inflammatory treatment is the primary and vital therapeutic approach for active, moderate-to-severe thyroid eye disease (TED). Accurate pretreatment prediction of treatment response is of paramount importance for the prognosis of patients. However, relying solely on the clinical activity score asa determinant of activity has led to unsatisfactory treatment outcomes. In recent years, significant advancements have been made in identifying predictive markers for anti-inflammatory treatment response in TED, clinical markers, body fluid biomarkers and imaging biomarkers. Several clinical studies have developed prediction models based on these markers. However, there is still a lack of comprehensive elucidation or comparison between the different markers. Therefore, this review aims to provide a detailed analysis of the definition, characteristics, and application of predictive markers for anti-inflammatory treatment response in TED. Through detailed literature search, 26 articles applying anti-inflammatory treatment effect prediction with a total of 1948 TED patients were used for analysis and discussion. By gaining a better understanding of the current research on predictive markers, we can accelerate and guide the exploration of treatment prediction strategies, leading us towards an era of precise therapy for TED.

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“…In the in vivo model, the early phase of EO in particular is characterized by overexpression of the proinflammatory cytokines Interferon-γ (IFN-γ) and TNF-α [127]. Even technetium-99 m (99 mTc) anti-TNF-α scintigraphy found TNF-α to be significantly increased in active EO [128]. Compared to the success of anti-TNF-αtreatment in rheumatoid arthritis and uveitis, despite the basic research evidence, there are few studies that have investigated the effects of TNF-α-blockade in EO.…”

Section: Tnf-α-blockermentioning

confidence: 99%

“…Gerade die Frühphase der EO ist im In-vivo-Modell gekennzeichnet durch Überexpression der proinflammatorischen Zytokine Interferon-γ (IFN-γ) und TNF-α [127]. Selbst in einer 99 mTc-Anti-TNF-α-Szintigrafie (99 mTc: Technetium-99 m) konnten signifikant erhöhte Anreicherungen bei aktiver EO nachgewiesen werden [128]. Im Vergleich zum Siegeszug der Anti-TNF-α-Therapie bei Rheumatoider Arthritis und Uveitis gibt es trotz der Evidenz aus der Forschung nur wenige Studien, die den Effekt der TNF-α-Blockade bei der EO untersucht haben.…”

Section: Tnf-α-blockerunclassified

Aktuelle Therapieansätze der endokrinen Orbitopathie – sind die zielgerichteten Therapien die Zukunft?

Eckstein,

Stöhr,

Görtz

et al. 2023

Klin Monbl Augenheilkd

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Die Endokrine Orbitopathie (EO) ist eine Autoimmunerkrankung der Augenhöhle die am allerhäufigsten im Zusammenhang mit einer Schilddrüsenautoimmunerkrankung vom Typ Basedow auftritt. Für die Diagnose spezifisch und für die Pathogenese von zentraler Bedeutung ist das Auftreten von gegen den TSH-Rezeptor gerichteten Autoantikörpern (TRAK). Diese Autoantikörper, zumeist mit stimulierender Wirkung, induzieren eine unkontrollierte Schilddrüsenüberfunktion und in der Augenhöhle einen Gewebeumbau und eine mehr oder weniger ausgeprägte Entzündung. In Folge kommt es im variablen Ausmaß zu entzündlicher Schwellung periokulär, Exophthalmus, und Fibrose der Augenmuskeln und dadurch zu einer Störung der symmetrischen Augenbeweglichkeit mit Doppelbildwahrnehmung. In den letzten Jahrzehnten umfassten die therapeutischen Anstrengungen für die entzündliche Orbitopathie allgemein immunsuppressive Maßnahmen und für die Schilddrüsenüberfunktion die symptomatische Therapie durch Hemmung der Schilddrüsenhormonproduktion. Mit dem Bekanntwerden, dass durch die TRAK auch ein wichtiger Wachstumsfaktorrezeptor aktiviert wird, der IGF1R (Insulin like growth factor 1 Rezeptor), wurden Biologika entwickelt, die diesen blockieren. Teprotumumab ist bereits in den USA zugelassen und die Therapieeffekte sind v.a. hinsichtlich der Exophthalmusreduktion enorm. Nebenwirkungen, v.a. Hyperglykämie und Hörstörungen sind zu beachten. Inwieweit die Autoimmunreaktionen (Produktion der TRAK/Anlocken von immunkompetenten Zellen) durch diese Therapien auch beeinflusst werden, ist noch nicht ausreichend geklärt. Rezidive nach der Therapie zeigen, dass die Hemmung der Autoimmunreaktion im Therapiekonzept insbesondere bei schwerem Verlauf mit enthalten sein muss. Graves’ orbitopathy is an autoimmune disease of the orbit that occurs most frequently with Graves’ hyperthyroidism. The occurrence of autoantibodies directed against the TSH receptor (TRAb) is of central importance for the diagnosis and for the pathogenesis. These autoantibodies, mostly with a stimulating effect, induce uncontrolled hyperthyroidism and tissue remodelling in the orbit and a more or less pronounced inflammation. Consequently, patients suffer in a variable extent from periocular swelling, exophthalmos, and fibrosis of the eye muscles and thus a restrictive motility impairment with double vision. In recent decades, therapeutic efforts mainly comprised immunosuppressive treatments and antithyroid drug therapy for hyperthyroidism to inhibit thyroid hormone production. With the detection that TRAb also activates an important growth factor receptor, IGF1R (insulin-like growth factor 1 receptor), biological agents have been developed. Teprotumumab (an inhibitory IGF1R antibody) has already been approved in the USA and the therapeutic effects are enormous, especially with regard to the reduction of exophthalmos. Side effects are to be considered, especially hyperglycaemia and hearing loss. If the autoimmune reaction (development of the TRAb/attraction of immunocompetent cells) is also influenced by anti IGF1R inhibiting agents, has yet to be sufficiently clarified. Recurrences after therapy show, that the inhibition of the antibody development must be included in the therapeutic concept, especially in severe cases.

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Technetium‐99m‐anti‐tumour necrosis factor alpha scintigraphy as promising predictor of response to corticotherapy in chronic active Graves' ophthalmopathy

Cited by 6 publications

References 30 publications

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

Radioimmune Imaging of α4β7 Integrin and TNFα for Diagnostic and Therapeutic Applications in Inflammatory Bowel Disease

Predictive markers for anti-inflammatory treatment response in thyroid eye disease

Aktuelle Therapieansätze der endokrinen Orbitopathie – sind die zielgerichteten Therapien die Zukunft?

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