Radionuclide Imaging of Cytotoxic Immune Cell Responses to Anti-Cancer Immunotherapy

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8+ T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided

Radionuclide imaging of cytotoxic immune cell responses to anti-cancer immunotherapy

Cancer immunotherapy is an evolving and promising cancer treatment that takes advantage of the body’s immune system to yield effective tumor elimination. Importantly, immunotherapy has changed the treatment landscape for many cancers, resulting in remarkable tumor responses and improvements in patient survival. However, despite impressive tumor effects and extended patient survival, only a small proportion of patients respond, and others can develop immune-related adverse events associated with these therapies, which are associated with considerable costs. Therefore, strategies to increase the proportion of patients gaining a benefit from these treatments and/or increasing the durability of immune-mediated tumor response are still urgently needed. Currently, measurement of blood or tissue biomarkers has demonstrated sampling limitations, due to intrinsic tumor heterogeneity and the latter being invasive. In addition, the unique response patterns of these therapies are not adequately captured by conventional imaging modalities. Consequently, non-invasive, sensitive, and quantitative molecular imaging techniques, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT) using specific radiotracers, have been increasingly used for longitudinal whole-body monitoring of immune responses. Immunotherapies rely on the effector function of CD8(+) T cells and natural killer cells (NK) at tumor lesions; therefore, the monitoring of these cytotoxic immune cells is of value for therapy response assessment. Different immune cell targets have been investigated as surrogate markers of response to immunotherapy, which motivated the development of multiple imaging agents. In this review, the targets and radiotracers being investigated for monitoring the functional status of immune effector cells are summarized, and their use for imaging of immune-related responses are reviewed along their limitations and pitfalls, of which multiple have already been translated to the clinic. Finally, emerging effector immune cell imaging strategies and future directions are provided

Myocardial microangiopathy associated with antiphospholipid antibodies.

Myocardial thrombotic microangiopathy is a well described post-mortem finding in patients with the catastrophic antiphospholipid (APL) syndrome. However, it has been only very rarely imaged in living patients. Here, we report two patients with APL antibodies presenting with scintigraphic, electrocardiographic and/or echocardiographic evidence of (sub)acute myocardial ischaemia, despite a normal coronary angiography. Formal proof of a thrombotic microangiopathy was obtained by a kidney biopsy in one patient. We emphasize the value of 99mTc-MIBI (2-methoxy isobutyl isonitrile) exercise stress myocardial scintigraphy for the detection of cardiac microangiopathy associated with the APL syndrome

Practical and operational considerations related to paediatric oral drug formulation : an industry survey

For over 15 years, US and EU regulations ensure that medicines developed for children are explicitly authorised for such use with age-appropriate forms and formulations, implying dedicated research. To shed light on how these regulations have been adopted by pharmaceutical companies and how various aspects of paediatric oral drug formulation development are currently handled, an exploratory survey was conducted. Topics included: general company policy, regulatory aspects, dosage form selection, in-vitro, in-silico and (non-)clinical in-vivo methods, and food effects assessment. The survey results clearly underline the positive impact of the paediatric regulations and their overall uptake across the pharmaceutical industry. Even though significant improvements have been made in paediatric product development, major challenges remain. In this respect, dosage form selection faces a discrepancy between the youngest age groups (liquid products preference) and older subpopulations (adult formulation preference). Additionally, concerted research is needed in the development and validation of in-vitro tools and physiology based pharmacokinetic models tailored to the paediatric population, and in estimating the effect of non-standard and paediatric relevant foods. The current momentum in paediatric drug development and research should allow for an evolution in standardised methodology and guidance to develop paediatric formulations, which would benefit pharmaceutical industry and regulators

Preventie en behandeling van A/H1N1-influenza bij patiënten met immuungemedieerde inflammatoire aandoeningen onder immunotherapie

Immuungemedieerde inflammatoire aandoeningen (IMID) vormen een heterogene groep van aandoeningen, waaronder chronische artritis, reumatische systeemziekten, inflammatoire darmziekten en psoriasis, met een gemeenschappelijke immunologische pathogenese en een gelijkaardige behandelingsstrategie, waaronder immunosuppressieve of immunomodulatoire middelen (immunotherapie). Immunotherapie omvat naast corticosteroïden en conventionele middelen zoals methotrexaat ook zogenaamde „targeted therapies” of „biologicals” (o.a. de tumornecrosisfactor(TNF)-remmers). IMID-patiënten onder immunotherapie zijn vatbaarder voor infecties en vormen een risicogroep in de context van de A/H1N1-influenzapandemie. Naar aanleiding van de verwachte pandemie met A/H1N1 werd een Belgische ad-hocwerkgroep opgericht die aanbevelingen formuleerde in verband met de preventie en de behandeling van A/H1N1-influenza voor deze risicogroep. Dit artikel vat de wetenschappelijke evidentie samen waarop deze aanbevelingen gebaseerd zijn. Naast de klassieke hygiënische maatregelen (hand- en hoesthygiëne, vermijding van contact met zieken) wordt aanbevolen deze patiënten te vaccineren tegen influenza (zowel de klassieke seizoensgriep als het type A/H1N1) en pneumokokken. Als risicopatiënten komen zij ook in aanmerking voor behandeling met virusremmers in geval van griepsymptomen. Immunotherapie (met uitzondering van corticosteroïden) dient tijdelijk onderbroken te worden bij een acute infectieuze opstoot

Values of neutral endopeptidase 24.11 as a tubular marker in human renal interstitial fibrosis with tubular atrophy

American Society of Nephrology (Orlando, 26-29 octobre 1994)info:eu-repo/semantics/publishe