Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D₂ and D₃ receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (¹¹C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14–30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20–30 min; spleen as reference region) demonstrated a statistically significant reduction (−36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20–30 min) (R² = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20–30 min) (R² = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20–30 min) (R² = 0.57, P = 0.05), nor did mean baseline proinsulin (R² = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D₃ receptor and dopamine D₂ receptor in HCs. No colocalization of the dopamine D₃ receptor or dopamine D₂ receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D₃ receptor, dopamine D₂ receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D₃ receptor and dopamine D₂ receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for ¹¹C-(+)-PHNO, a dopamine D₃ receptor–preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.

传统上，1型糖尿病（T1DM）的特征是β细胞团块（BCM）完全被破坏。但是，越来越多的证据表明T1DM中可能存在残留的BCM。鉴于缺乏用于测量BCM的体内工具，β细胞功能（例如C肽释放）的常规临床测量可能无法反映BCM。我们先前证明了使用多巴胺D ₂和D ₃受体激动剂3,4,4a，5,6,10b-hexahydro-2 H-萘[1,2- b ] [1,4]恶嗪进行PET成像的潜在效用-9-ol（¹¹ C-（+）-PHNO）区分健康对照（HC）和T1DM个体。方法：16个人参加了会议（10名男性，6名女性； 9个HC，7个T1DM）。糖尿病的平均病程为18±6年（范围14至30年）。对个体进行PET / CT扫描，并以胰腺为中心进行120分钟的动态PET扫描。一室和两室模型用于估计胰腺和脾脏分布量。还研究了参考区域的方法（以脾脏为参考）。定量的PET测量与临床结果测量相关。进行免疫组织化学检查多巴胺受体与内分泌激素在HC和T1DM胰腺组织中的共定位。结果：在任何T1DM个体中均未检测到C肽释放，而在5个T1DM个体中有3个检测到胰岛素原。胰腺SUV比值减1（SUVR-1）（20–30分钟；脾脏作为参考区域）显示放射性配体结合具有统计学显着性降低（-36.2％）（HCs，5.6； T1DMs，3.6；P = 0.03）。诊断时的年龄与胰腺SUVR-1（20-30分钟）显着相关（R ² = 0.67，P = 0.025）。糖尿病持续时间与胰腺SUVR-1（20-30分钟）没有显着相关性（R ² = 0.36，P = 0.16）。在最大血糖增强时，对精氨酸的平均急性C肽反应与SUVR-1（20-30分钟）无显着相关性（R ²= 0.57，P = 0.05），也没有基线胰岛素原（R ² = 0.45，P = 0.10）。免疫组织化学表明，HCs中多巴胺D ₃受体和多巴胺D ₂受体共定位。生长抑素，胰高血糖素或多肽Y未见多巴胺D ₃受体或多巴胺D ₂受体共定位。在单独的T1DM个体中，多巴胺D ₃受体，多巴胺D ₂受体或胰岛素抗体未见免疫染色。内分泌多巴胺D ₃受体和多巴胺D _2的丧失受体表达伴随着β细胞功能性胰岛素分泌能力的丧失。结论： 30分钟的扫描时间和SUVR-1为¹¹ C-（+）-PHNO（一种多巴胺D ₃受体优先激动剂PET放射性配体）提供了定量的结局指标，以区分T1DM和HCs中的BCM。