99mTc-HMPAOを用いた脳血流の簡便な定量的評価法 -Patlak Plot法における手技的,原理的考察-

金沢大学大学院医学系研究

Prediction of myocutaneous adverse side effect due to intra-arterial chemotherapy by intra-arterial 99mTc-macroaggregated albumin administration in patients with bone and soft-tissue tumors

金沢大学大学院医学系研究科In malignant bone and soft-tissue tumors, intra-arterial chemotherapy and limb-saving surgery have become popular. Myocutaneous inflammatory change and necrosis are the major local side effects of intra-arterial chemotherapy. 99mTc-macroaggregated albumin (MAA) imaging with intra-arterial tracer administration was performed to evaluate drug distribution, and the ability of 99mTc-MAA imaging to predict local side effects was assessed. Methods: In 24 patients, 42 99mTc-MAA images were obtained with tracer injection through an intra-arterial catheter that was inserted into the proximal portion of the tumor-feeding artery. Abnormal uptake other than by tumor was assessed visually and quantitatively. Results: In visual analysis, abnormal 99mTc-MAA accumulation was observed in 21 of 42 images. In the first consecutive 13 of these 21 images, intra-arterial chemotherapy with cisplatin, doxorubicin, and caffeine was administered, and myocutaneous inflammation or necrosis in the area corresponding to the abnormal 99mTc-MAA uptake was observed in 11. In contrast, none of the 21 images without abnormal 99mTc-MAA uptake demonstrated any local adverse effect from intra-arterial chemotherapy. In the last consecutive 8 images with abnormal 99mTc-MAA uptake, intra-arterial chemotherapy was initiated with only cisplatin, and doxorubicin and caffeine administration was changed to the intravenous route. In all 8 of these images, no local adverse effects from chemotherapy were observed. Overall, the sensitivity, specificity, and accuracy of 99mTc-MAA imaging for the detection of myocutaneous damage were 100% (11/11), 91% (21/23), and 94% (32/34), respectively, and positive and negative predictive values were 85% (11/13) and 100% (21/21), respectively. In quantitative analysis, when the diagnostic threshold of the uptake ratio was set at 2.5, sensitivity, specificity, and accuracy for the detection of myocutaneous complications were 91% (10/11), 96% (22/ 23), and 94% (32/34), respectively, and positive and negative predictive values were 91% (10/11) and 96% (22/23), respectively. Conclusion: 99mTc-MAA imaging with intra-arterial infusion before intra-arterial chemotherapy for bone and soft-tissue tumors can facilitate prediction of local myocutaneous adverse effects due to chemotherapy

Early prediction of histopathological tumor response to preoperative chemotherapy by Tc-99m MIBI imaging in bone and soft tissue sarcomas

金沢大学附属病院核医学診療科PURPOSE: Tc-99m-methoxyisobutylisonitrile (MIBI) accumulates in only viable cells. In patients with bone and soft tissue sarcomas, preoperative chemotherapy is essential and the early prediction of the tumor response to chemotherapy would be beneficial for the planning of treatment strategy. The purpose of this study was to assess whether the change of Tc-99m-MIBI images from the prechemotherapy state to the early to midportion of chemotherapy can predict the final histopathological tumor response as accurately as the change of imaging after completion of chemotherapy. METHODS: Seventy-three patients with bone and soft tissue sarcomas underwent Tc-99m-MIBI scintigraphy before chemotherapy and at least 2 times after the second or third or fifth course of chemotherapy. The changes of the tracer uptake (ΔUR) and perfusion (ΔPI) from prechemotherapy to postchemotherapy were compared with histologic response. RESULTS: The sensitivity, specificity, and accuracy for the prediction of effective chemotherapy in ΔPI were 88%, 83%, 85% after second, 85%, 72%, 78% after third, and 81%, 71%, 76% after 5th chemotherapy, and those in ΔUR were 88%, 83%, 85% after 2nd, 85%, 92%, 89% after 3rd, and 94%, 77%, 85% after fifth chemotherapy, respectively. The area under the receiver operator characteristic curve of the ΔPI after second, third, and fifth chemotherapy were similarly good (0.842, 0.858, 0.811, respectively) and those of ΔUR were similarly excellent (0.915, 0.936, 0.931, respectively). CONCLUSION: In patients with bone and soft tissue sarcomas, the change of Tc-99m-MIBI images from prechemotherapy to early to middle of chemotherapy can predict the final histopathological tumor response to chemotherapy as accurately as the change of Tc-99m-MIBI images from prechemotherapy to the completion of the preoperative chemotherapy. © 2010 by Lippincott Williams & Wilkins

Prognostic value of Tc-99m-MIBI performed during middle course of preoperative chemotherapy in patients with malignant bone and soft-tissue tumors

Purpose: This study was aimed to determine whether Tc-99m-hexakis-2- methoxyisobutylisonitrile (MIBI) scintigraphy performed in the middle of preoperative chemotherapy has a prognostic value in patients with malignant bone and soft tissue tumors (MBST). Materials and Methods: In 90 patients with MBST, Tc-99m-MIBI scintigraphy was performed 15 minutes after tracer injection before the first and after the third chemotherapy cycles. After 5 cycles of chemotherapy and tumor resection, therapeutic effect was assessed by histopathology. The percent reduction of uptake ratio (AUR) was calculated according to the following equation: 100 × ([prechemotherapy UR - post-middle course of chemotherapy UR]/prechemotherapy UR). Results: The average follow-up for the entire population was 52 months. Twenty-one patients had clinically detectable metastases at initial presentation (primary metastasis). Kaplan-Meier analysis demonstrated that absence of metastasis was associated with good survival in all patients, in patients with bone tumor, and those with soft tissue tumor (P < 0.0001, P < 0.0001, and P = 0.0003, respectively), and AUR ≥30% was also associated with survival in all patients and patients with bone tumor (P = 0.011 and P = 0.047, respectively), but was marginal in those with soft tissue tumor (P = 0.091). Multivariate analysis showed that primary metastasis was the most powerful independent predictor of a lethal clinical outcome in all patients, in both patients with bone and soft tissue tumors (hazard ratio [HR]: 4.9, 95% confidence interval [CI]: 2.61-9.08, P < 0.0001; HR: 15.1, CI: 4.86-52.7, P < 0.0001; HR: 3.7, CI: 1.45-8.94, P = 0.0069, respectively) and showed that Tc-99m-MIBI scintigraphy had a good independent long-term prognostic value in all patients and patients with bone tumor (HR: 2.2, CI: 1.14-4.43, P = 0.017; HR: 6.0, CI: 2.01-21.6, P = 0.0009, respectively) but not in those with soft tissue tumor (HR: 1.5, CI: 0.61-4.09, P = 0.38). Good disease-free survival was associated with ΔUR §30% in all patients and patients with soft tissue tumor (P = 0.0093 and P = 0.017, respectively) but not in those with bone tumor (P = 0.19). Conclusions: Tc-99m-MIBI scintigraphy at the middle course of preoperative chemotherapy could be used as a prognostic indicator in patients with MBST. Copyright © 2012 by Lippincott Williams & Wilkins.Thesis of Hiroshi Wakabayashi / 博士学位論文 若林 大

コリン作動性中枢神経支配の核医学的画像化の基礎的研究：アルツハイマー病動物モデルにおける神経伝達物質および受容体の変化

金沢大学大学院医学系研究

アルツハイマー病動物モデルの作製とその評価法

金沢大学大学院医学系研究

新規シグマ受容体分子イメージング剤による「痴呆の進行・治療指針予測」に関する研究

金沢大学医学部附属病院我々はアセチルコリントランスポーター(VAChT)分子イメ-ジング剤の開発のためにVAChTに高い親和性を示すベサミコールを基本化合物として多くの類似体について検討を行ってきた。その過程でベサミコールのパラ位にヨウ素のような小さい官能基を導入することにより、VAChT親和性が減少する一方、シグマ受容体に対して高親和性を示すことがわかった。そこで本研究はの目的は、ポジトロン核種であるC-11の導入可能なパラ位にメチル基を導入した[^C](+)-P-チルベサミコール((+)-PMV)を設計し、[^C]-(+)-PMVのPET用シグマ受容体分子イメージング剤としての可能性を検討することにある。本年はまず、ポジトロン核種であるC-11の導入を容易にするため、ベサミコールのパラ位にメチル基を導入した(+)-para-imethylvesamicol[(+)PMV]の合成を検討した。合成は、4-bromobenzaldehyde(1)を出発原料として、アルデヒドの保護、グリニヤー反応等により4-methylbenzaldehyde(2)を合成する。2から5工程でベサミコール誘導体合成の際の基本構造体である4-(4-metylphenyl)piperidine(3)を合成した。目的の(+)PMVは3か2工程で合成できた。最終的に出発原料1から10行程で目的の(+)PMVを通算収率2.5%で得ることができた、構造はNMR,質量分析、元素分析により確認した。次に、(+)PMVのシグマー1,2受容体及びVAChTに対する親和性を調べるためラット脳のP2分画を用いたインビトロ薬物阻害実験を行った。その結果、(+)-PMVの各受容体への親和性はσ-1受容体(Ki=3.0nM)、σ-2受容体(Ki=40.7nM)、VAChT(Ki=199nM)であり、σ-1受容体にのみ高い親和性を示した。C-11標識化のための前駆体であるトリブチルスズ体はp-iodovesamicolから合成した。[^C](+)PMVはトリブチルスズ前駆体と[^C]CH_3Iのクロスカップリング反応により、[^C]CH_3Iに対し放射化学的収率38%、比放射能は11 TBq/mmol(EOB後30分)で合成した。以上、(+)PMVはシグマ受容体に選択的に高い親和性を持ち、トリブチルスズ前駆体から容易に[^C](+)PMVを合成することができた。来年度は[^C](+)PMVのPET用シグマ受容体分子イメージング剤として可能性を動物実験により検討する予定である。研究課題/領域番号:17591254, 研究期間(年度):2005 – 2006出典：「新規シグマ受容体分子イメージング剤による「痴呆の進行・治療指針予測」に関する研究」研究成果報告書　課題番号17591254（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-17591254/)を加工して作