Pig islets are an alternative source for islet transplantation to treat type 1 diabetes (T1D), but reproducible curative potential in the pig-to-nonhuman primate (NHP) model has not been demonstrated. Here, we report that pig islet grafts survived and maintained normoglycemia for >6 months in four of five consecutive immunosuppressed NHPs. Pig islets were isolated from designated pathogen-free (DPF) miniature pigs and infused intraportally into streptozotocin-induced diabetic rhesus monkeys under pretreatment with cobra venom factor (CVF), anti-thymocyte globulin (ATG) induction and maintenance with anti-CD154 monoclonal antibody and low-dose sirolimus. Ex vivo expanded autologous regulatory T cells were adoptively transferred in three recipients. Blood glucose levels were promptly normalized in all five monkeys and normoglycemia (90-110 mg/dL) was maintained for >6 months in four cases, the longest currently up to 603 days. Intravenous glucose tolerance tests during the follow-up period showed excellent glucose disposal capacity and porcine C-peptide responses. Adoptive transfer of autologous regulatory T cells was likely to be associated with more stable and durable normoglycemia. Importantly, the recipients showed no serious adverse effects. Taken together, our results confirm the clinical feasibility of pig islet transplantation to treat T1D patients without the need for excessive immunosuppressive therapy.
Single-photon emission computed tomography/computed tomography (SPECT/CT) is an already established nuclear imaging modality. Co-registration of functional information (SPECT) with anatomical images (CT) paved the way to the wider application of SPECT. Recent advancements in quantitative SPECT/CT have made it possible to incorporate quantitative parameters, such as standardized uptake value (SUV) or %injected dose (%ID), in gamma camera imaging. This is indeed a paradigm shift in gamma camera imaging from qualitative to quantitative evaluation. In fact, such quantitative approaches of nuclear imaging have only been accomplished for positron emission tomography (PET) technology. Attenuation correction, scatter correction, and resolution recovery are the three main features that enabled quantitative SPECT/CT. Further technical improvements are being achieved for partial-volume correction, motion correction, and dead-time correction. The reported clinical applications for quantitative SPECT/CT are mainly related to Tc-99m-labeled radiopharmaceuticals: Tc-99m diphosphonate for bone/joint diseases, Tc-99m pertechnetate for thyroid function, and Tc-99m diethylenetriaminepentaacetic acid for measurement of glomerular filtration rate. Dosimetry before trans-arterial radio-embolization is also a promising application for Tc-99m macro-aggregated albumin. In this review, clinical applications of Tc-99m quantitative SPECT/CT will be discussed.
BACKGROUND AND PURPOSE: Nigrostriatal dopaminergic function in patients with Parkinson disease can be assessed using 123 I-2b -carbomethoxy-3b -(4-iodophenyl)-N-(3-fluoropropyl)-nortropan dopamine transporter ( 123 I-FP-CIT) SPECT, and a good correlation has been demonstrated between nigral status on SWI and dopaminergic denervation on 123 I-FP-CIT SPECT. Here, we aim to correlate quantified dopamine transporter attenuation on 123 I-FP-CIT SPECT with nigrosome-1 status using susceptibility map-weighted imaging (SMWI).
MATERIALS AND METHODS:Between May 2017 and January 2018, consecutive patients with idiopathic Parkinson disease (n ¼ 109) and control participants (n ¼ 29) who underwent 123 I-FP-CIT SPECT with concurrent 3T SWI were included. SMWI was generated from SWI. Two neuroradiologists evaluated nigral hyperintensity from nigrosome-1 on each side of the substantia nigra. Using consensus reading, we compared the 123 I-FP-CIT-specific binding ratio according to nigral hyperintensity status and the 123 I-FP-CIT specific binding ratio threshold to confirm the loss of nigral hyperintensity was determined using receiver operating characteristic curve analysis.
RESULTS:The concordance rate between SMWI and 123 I-FP-CIT SPECT was 65.9%. The 123 I-FP-CIT-specific binding ratios in the striatum, caudate nucleus, and putamen were significantly lower when nigral hyperintensity in the ipsilateral substantia nigra was absent than when present (all, P , .001). The 123 I-FP-CIT-specific binding ratio threshold values for the determination of nigral hyperintensity loss were 2.56 in the striatum (area under the curve, 0.890), 3.07 in the caudate nucleus (0.830), and 2.36 in the putamen (0.887).CONCLUSIONS: Nigral hyperintensity on SMWI showed high positive predictive value and low negative predictive value with dopaminergic degeneration on 123 I-FP-CIT SPECT. In patients with Parkinson disease, the loss of nigral hyperintensity is prominent in patients with lower striatal specific binding ratios. ABBREVIATIONS: PD ¼ Parkinson disease; SBR ¼ specific binding ratio; SMWI ¼ susceptibility map-weighted imaging; SN ¼ substantia nigra; 123 I-FP-CIT ¼ 123 I-2[b ]-carbomethoxy-3[b ]-(4-iodophenyl)-N-(3-fluoropropyl)-nortropan dopamine transporter; MMSE ¼ Mini-Mental State Examination; MoCA ¼ Montreal Cognitive Asses; UPDRS ¼ Unified Parkinson's Disease Rating Scale; ROC ¼ receiver operating characteristic; AUC ¼ area under the curve
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