Although multifunctional inorganic nanoparticles have been extensively explored for effective cancer diagnosis and therapy, their clinical translation has been greatly impeded because of significant uptake in the reticuloendothelial system and concerns about potential toxicity. In this study, we uncovered the thermosensitive biodegradability of CuS nanoparticles, which have classically been considered as stable in bulk state. Polyethylene glycol (PEG)-coated CuS nanoparticles (CuS-PEG) were well preserved at 4 ºC but were rapidly degraded at 37 ºC within 1 week in both in vitro and in vivo tests. Furthermore, real-time multispectral optoacoustic tomography, which is more convenient and accurate than traditional ex vivo analysis, was successfully employed to noninvasively demonstrate the biodegradability of CuS-PEG nanoparticles and dynamically monitor their tumor imaging capacity. The temperature-dependent controllable degradation profile and excellent tumor retention of CuS-PEG nanoparticles endows them with great potential for clinical applications since it ensures that the nanoparticles remain intact during production, transportation, and storage but degrade and clear from the body at physiological temperature after accomplishing sufficient diagnosis and therapeutic operations.

Exosomes have attracted tremendous attention due to their important role in physiology, pathology, and oncology, as well as promising potential in biomedical applications. Although great efforts have been dedicated to investigating their biological properties and applications as natural cancer drug-delivery systems, the systemic biodistribution of exosomes remains underexplored. In addition, exosome-based drug delivery is inevitably hindered by the robust liver clearance, leading to suboptimal tumor retention and therapeutic efficiency. In this study, we report one of the first examples using in vivo positron emission tomography (PET) for noninvasive monitoring of copper-64 (64Cu)-radiolabeled polyethylene glycol (PEG)-modified exosomes, achieving excellent imaging quality and quantitative measurement of blood residence and tumor retention. PEGylation not only endowed exosomes with a superior pharmacokinetic profile and great accumulation in the tumor versus traditionally reported native exosomes but also reduced premature hepatic sequestration and clearance of exosomes, findings that promise enhanced therapeutic delivery efficacy and safety in future studies. More importantly, this study provides important guidelines about surface engineering, radiochemistry, and molecular imaging in obtaining accurate and quantitative biodistribution information on exosomes, which may benefit future exploration in the realm of exosomes.

Immunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) due to the presence of an immunosuppressive tumor-associated stroma. Here, we demonstrate an effective modulation of that stroma by irreversible electroporation (IRE), a local ablation technique that has received regulatory approval in the United States. IRE induces immunogenic cell death, activates dendritic cells, and alleviates stroma-induced immunosuppression without depleting tumor-restraining collagen. The combination of IRE and anti-programmed cell death protein 1 (anti-PD1) immune checkpoint blockade promotes selective tumor infiltration by CD8+ T cells and significantly prolongs survival in a murine orthotopic PDAC model with a long-term memory immune response. Our results suggest that IRE is a promising approach to potentiate the efficacy of immune checkpoint blockade in PDAC.

607 Objectives: Exciting progress has been made in cancer immunotherapy with immune checkpoint blockade antibodies. Noninvasive imaging of PD-1 and PD-L1 at high sensitivity and selectivity could be useful in cancer detection and monitoring treatment response. However, detection of pancreatic ductal adenocarcinoma (PDAC) tumor in the pancreas with immunoradiotracers has been challenging due to high uptakes of antibodies in the spleen and the liver. The purpose of this study is to investigate whether it is feasible to image orthotopic PDAC tumors by PET. Methods: 64Cu was labeled to anti-PD-L1, anti-PD-1, and their isotype-matched IgGs through chelator 1,4,7-Triazacyclononane-1,4,7-triacetic acid (NOTA). 64Cu-labeled antibodies were intravenously injected to C57BL/6 mice bearing orthotopic KRAS[asterisk] PDAC tumors. Mice were dissected at 24 h post-injection, and biodistribution of the antibodies in blood, tumor and other organs were quantified. MicroPET/CT images were acquired using 64Cu-NOTA-anti-PD-L1 with or without co-injection of cold anti-PD-L1. In vivo organ uptakes of anti-PD-L1 were analyzed by quantifying PET images (Fig C). Results: Distribution pattern of anti-PD-1 was similar to that of its corresponding IgG control. In comparison, the blood activity of anti-PD-L1 was only 5% that of its IgG control. Tumor-to-blood ratio of anti-PD-L1 was more than 40 times higher than that of anti-PD-1 and IgG controls. The uptakes of anti-PD-L1 in the liver, spleen, brown adipose tissue, and lymph nodes were significantly higher than that of its IgG control (p< 0.05). MicroPET imaging with 64Cu-anti-PD-L1 in mice bearing orthotopic KRAS[asterisk] tumors showed strong signals in the spleen and weak signals in the tumor (Fig A). However, by co-injection of the radiotracer with cold anti-PD-L1, the tumor was clearly visualized due to markedly reduced signals in the spleen and increased radioactivity in the tumor (Fig B). Ex vivo distribution in subcutaneous KRAS[asterisk] PDAC model revealed that blocking with cold antibody elevated tumor-to-spleen ratio from 0.85 to 4.5. Conclusions: These data suggested that co-injection with cold anti-PD-L1 prevented entrapment of 64Cu-anti-PD-L1 in the spleen, prolonged its blood retention, and thereby successfully led to its accumulation in KRAS[asterisk] tumor.

349 Objectives: Exosomes, the naturally secreted lipid vesicles carrying myriad cellular proteins and genetic information, have recently attracted tremendous attention. Due to its extremely high biocompatibility and role in in cancer progression, exosomes have been considered as a promising natural nanoplatform for drug delivery and immunotherapy of cancer. However, a majority of the exosomes injected systemically are cleared by the liver with suboptimal tumor retention, impeding their potential application and clinical translation in cancer treatment. The goal of this study is to design radiolabeled PEGylated exosomes to improve tumor retention and systematically delineate their biodistribution via PET imaging. Methods: Exosomes were generated from 4T1 murine triple negative breast cancer cells by centrifuging conditioned cell culture medium at different velocities. As-prepared exosome was then reacted with polyethylene glycol (PEG) to form exosome-PEG, and characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-VIS spectrometry. Exosome and exosome-PEG were radiolabeled and their radiolabeling efficiency and stability were measured by thin-layer chromatography (TLC). Radiolabeled exosome and exosome-PEG were injected into 4T1 tumor-bearing mice for in vivo PET imaging and biodistribution studies. The imaging results were validated by histological analysis with fluorescence-labeled exosomes. Results: 4T1-derived exosome and exosome-PEG were generated with size ~70 nm in diameter. After radiolabeling, 95.6 ± 0.3 % and 97.7 ± 0.2 % of the nuclides were successfully labeled on exosome and exosome-PEG, respectively, suggesting excellent labeling efficiency. After incubation in serum for 24 h, greater than 80% and 90% of the nuclides remained stable on exosome or exosome-PEG, indicating their excellent stability in physiological environment. Serial PET imaging and biodistribution studies revealed a significantly higher tumor uptake and decreased liver sequestration of exosome-PEG, in comparison with exosome without PEG decoration, demonstrating enhanced tumor retention and reduced hepatic clearance after appropriate surface modification. Histological images of fluorescence-labeled exosome-PEG displayed that exosomes was able to extravasate from the vessels. Conclusion: Radiolabeled PEGylated exosomes were successfully prepared, which exhibited significantly enhanced tumor uptake and capacity for in vivo PET imaging of tumor. Surface modification with PEG reduced hepatic clearance of exosomes, which promises potential applications of exosomes in drug delivery and immunotherapy of cancer. The important insights provided by in vivo PET imaging of PEGylated exosomes are expected to guide future development of exosome-based drug delivery system. Acknowledgment: Supported in part by John S. Dunn Foundation.

Immunotherapy has only limited efficacy against pancreatic ductal adenocarcinoma (PDAC) because of the presence of an immunosuppressive tumor-associated stroma. Here, we showed that combined IRE and anti-PD-1 immune checkpoint blockade significantly suppressed tumor growth and prolonged the lives of immunocompetent mice bearing well-established orthotopic PDAC. Remarkably, more than 35% of mice had a durable response, and were found to be free of residual tumor upon necropsy. All mice that survived for 60 days after IRE and anti-PD1 treatments rejected tumor cell re-challenge. Analyses of splenocytes confirmed that these long-term survivors developed an anti-tumor memory T cell response. Further mechanistic studies unveiled that the efficacy of IRE + anti-PD-1 could be attributed to multiple factors, including rapid release of danger associated molecular patterns, activation of DCs, and alleviation of immunosuppressive tumor microenvironment. Neutralization of CD8+ T cells by anti-CD8 antibody nullified the antitumor effect of combined IRE and anti-PD-1, suggesting that tumor-infiltrating CD8+ T cells played a key role in mediating the anti-tumor efficacy of IRE + anti-PD-1.Given that both IRE and anti-PD-1 antibodies are already used in the clinic, our results support the translation of this combination as a promising approach for treating patients with PDAC. Citation Format: Jun Zhao, Xiaofei Wen, Tingting Li, Marites Melancon, Sanjay Gupta, Weiyi Peng, Chun Li. Irreversible electroporation induces immunogenic cell death and mediates durable response in orthotopic PDAC model in combination with anti-PD-1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4152.

329 Objectives: Copper sulfide nanoparticles (CuS NPs) have emerged as one of the most promising theranostic nanoplatforms for treating cancer, due to their relatively small size, facile chemistry, intrinsic biodegradability and excellent photothermal properties. Herein, we designed an anti-folate receptor 1 antibody-conjugated CuS NP (CuS-PEG-αFOLR1) through click chemistry. Our goal was to investigate its in vitro and in vivo targeting towards FOLR1-postive tumor (SKOV3 ovarian cancer) and its application in multispectral optoacoustic tomography (MSOT) as a novel nonradioactive cancer diagnosis paradigm. Methods: Polyethylene glycol (PEG)-coated CuS NPs were synthesized via one-step reaction using CuCl2 and Na2S as the precursors and mPEG-SH and NH2-PEG-SH as the surfactants at 95 oC. As-prepared CuS-PEG-NH2 was conjugated with a click chemistry compound trans-cyclooctene (TCO), while αFOLR1 and its isotype control IgG were conjugated with the corresponding click chemistry compound tetrazine (Tz). The resulting CuS-PEG-TCO was subsequently reacted with αFOLR1-Tz and IgG-Tz to form CuS-PEG-αFOLR1 or CuS-PEG-IgG for in vitro and in vivo experiments. The CuS nanoconjugates were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and UV-VIS-NIR spectrometry. Fluorescence-activated cell sorting (FACS) was performed to validate the targeting specificity of αFOLR1 and CuS-PEG-αFOLR1 in vitro. MSOT was carried out to noninvasively monitor the biodistribution of CuS-PEG-αFOLR1 and CuS-PEG-IgG and evaluate their tumor targeting efficacy in SKOV3 ovarian tumor-bearing mice. The imaging results were validated by histological analysis. Results: CuS-PEG-αFOLR1 and CuS-PEG-IgG were successfully synthesized with narrow size range (14~16 nm in diameter). After incubating with SKOV3 cells at 4 oC for one hour, αFOLR1 exhibited ~30 times higher cell uptake than its isotype control IgG, while CuS-PEG-αFOLR1 displayed ~3 times higher uptake than that of CuS-PEG-IgG. Successful blocking with an excess amount of αFOLR1 further confirmed the targeting specificity. In vivo MSOT studies revealed a significant enhancement of tumor uptake of CuS-PEG-αFOLR1 at various wavelengths (922 ± 116, 1052 ± 216,1136 ± 361 and 1050 ± 213 ΔMSOT a.u. at 800, 850, 900 and 950 nm), which was significantly higher than that of CuS-PEG-IgG (156 ± 241, 126 ± 263,143 ± 96 and 243 ± 307 ΔMSOT a.u. at 800, 850, 900 and 950 nm). In vitro and ex vivo histological examinations further confirmed the specificity of CuS-PEG-αFOLR1 for folate receptor 1 overexpressed cancer. Conclusion: In this study, we reported a novel nonradioactive αFOLR1-conjugated CuS NP, capable of targeting FOLR1 overexpressing SKOV3 tumor both in vitro and in vivo. MSOT imaging revealed significantly enhanced tumor uptake of CuS-PEG-αFOLR1 compared with CuS-PEG-IgG. The data presented here provides evidence for establishing CuS-PEG-αFOLR1 as a potential nanoplatform for molecular imaging and cancer theranostics. Acknowledgements:Supported in part by John S. Dunn Foundation.

Aim: To demonstrate the feasibility of intratracheal administration in orthotopic lung cancer model with 19 F MRI. Materials & methods: α v β 3 -integrin targeting ability of the perfluorocarbon (PFC) nanoparticles was tested. Orthotopic lung cancer model was established in rabbits under computed tomography guidance. α v β 3 -targeted PFC nanoparticles were administrated intratracheally or intravenously, and 19 F MRI was performed before and up to 24 h after administration. Results: The targeted PFC nanoparticles could bind with α v β 3 -integrin. PFC concentrations in the tumors of intratracheal group after administration were significantly higher than intravenous group. Conclusion: Intratracheal administration of PFC nanoparticles was shown to be feasible and efficacious. 19 F MRI with α v β 3 -targeted PFC nanoparticles provided quantitative assessment of nanoparticles distribution and tumor angiogenesis.

192 Objectives: Copper sulfide nanoparticles (CuS NPs) have emerged as one of the most promising theranostic nanoplatforms for treating cancer, due to their relatively small size, facile chemistry and excellent photothermal properties. Herein, we have designed a thermosenstive biodegradable CuS NP, which can be more clinical relevant with lower side effects. Our goal was to investigate its in vitro and in vivo biodegradation profile, and apply it to high-resolution multispectral optoacoustic tomography (MSOT) in living animals in both static and dynamic manners. Methods: Polyethylene glycol (PEG)-coated CuS NPs were synthesized via a one-step reaction with CuCl2 and Na2S as the precursors and mPEG-SH as the surfactant reacted at 90 oC. As-prepared CuS-PEG was incubated in water/PBS in different temperatures to examine its in vitro biodegradation by transmission electron microscopy (TEM), optical absorbance based on UV-VIS-NIFR spectrometry and ion concentration based on inductively coupled plasma optical emission spectrometry (ICP-OES). CuS-PEG was injected into healthy Balb/c mice, and livers of CuS-PEG NP-injected mice were investigated over time with ICP-OES for in vivo biodegradation. MSOT was performed in SKOV-3 tumor bearing nude mice to validate the imaging capacity of the biodegradable CuS NPs. Results: CuS-PEG NPs were successfully synthesized with superior solubility and size range 10~12 nm in diameter. After incubating with water/PBS for 7 days at 37 oC, significant degradation (73.2 ± 0.1 %) was observed; whereas minimal degradation (14.0 ± 0.3 %) was observed when incubating at 4 oC. Different conditions, such as air exposure and presence of residual precursors, were also investigated, suggesting that temperature is the major cause of biodegradation. Cu concentration in liver based on ICP-OES also demonstrated significant biodegradation (50.0 ± 0.4 μg NP per g tissue at 3 h p.i. v.s. 8.2 ± 0.4 μg NP per g tissue at 7 days p.i.) of CuS-PEG in vivo. Both static and dynamic MSOT showed manifestly enhanced signal in tumor after 2h p.i. which decreased with time, correlating with the in vitro findings. Of note, degraded Cu ions will not render MSOT signal, leading to more accurate imaging results in comparison to the imaging techniques that rely on radionuclides. Conclusions: In this study, we reported a novel biodegradable CuS NPs for MSOT in living animals, which are able to effectively enhance the tumor signal and promptly degrade in several days. The degradation is controllable and temperature-dependent, making it a clinically-translatable in vivo theranostic platform with lower long-term side effects. Our study provides a comprehensive and unique perspective to evaluate CuS NPs, and may inspire future explorations into the realm of more controllable, biodegradable, and clinical relevant nanotheranostics.

Eighty percent of lung cancers originate as subtle premalignant changes in the airway mucosal epithelial layer of bronchi and alveoli, which evolve and penetrate deeper into the parenchyma. Liquid-ventilation, with perfluorocarbons (PFC) was first demonstrated in rodents in 1966 then subsequently applied as lipid-encapsulated PFC emulsions to improve pulmonary function in neonatal infants suffering with respiratory distress syndrome in 1996. Subsequently, PFC nanoparticles (NP) were extensively studied as intravenous (IV) vascular-constrained nanotechnologies for diagnostic imaging and targeted drug delivery applications. Methods: This proof-of-concept study compared intratumoral localization of fluorescent paramagnetic (M) PFC NP in the Vx2 rabbit model using proton (1H) and fluorine (19F) magnetic resonance (MR) imaging (3T) following intratracheal (IT) or IV administration. MRI results were corroborated by fluorescence microscopy. Results: Dynamic 1H-MR and 19F-MR images (3T) obtained over 72 h demonstrated marked and progressive accumulation of M-PFC NP within primary lung Vx2 tumors during the first 12 h post IT administration. Marked 1H and 19F MR signal persisted for over 72 h. In contradistinction, IV M-PFC NP produced a modest transient signal during the initial 2 h post-injection that was consistent circumferential blood pool tumor enhancement. Fluorescence microscopy of excised tumors corroborated the MR results and revealed enormous intratumor NP deposition on day 3 after IT but not IV treatment. Rhodamine-phospholipid incorporated into the PFC nanoparticle surfactant was distributed widely within the tumor on day 3, which is consistent with a hemifusion-based contact drug delivery mechanism previously reported. Fluorescence microscopy also revealed similar high concentrations of M-PFC NP given IT for metastatic Vx2 lung tumors. Biodistribution studies in mice revealed that M-PFC NP given IV distributed into the reticuloendothelial organs, whereas, the same dosage given IT was basically not detected beyond the lung itself. PFC NP given IT did not impact rabbit behavior or impair respiratory function. PFC NP effects on cells in culture were negligible and when given IV or IT no changes in rabbit hematology nor serum clinical chemistry parameters were measured. Conclusion: IT delivery of PFC NP offered unique opportunity to locally deliver PFC NP in high concentrations into lung cancers with minimal extratumor systemic exposure.

原发性肝癌(Hepatocellular carcinoma,HCC)是肝脏最常见的恶性肿瘤,具有高发病率、死亡率及预后差的特点,大多数患者确诊时为进展期,已失去手术机会,严重危及患者生命.虽然目前相关的治疗方法较多,但预后仍较差,介入治疗作为一种微创疗法在提高患者生存期、改善患者生活质量等方面取得显著效果.本文就原发性肝癌的介入治疗现状与进展进行综述.

目的:探讨部分性脾动脉栓塞术(PSE)治疗原发性肝癌合并脾功能亢进的临床疗效及安全性.方法:选择2008年5月至2013年4月我科收治的160例原发性肝癌合并有脾功亢进患者为研究对象,患者在行肝动脉化疗栓塞术(TACE)的同时进行PSE,PSE栓塞面积在30％～60％之间,观察治疗后3天、7天、1个月、3个月、6个月患者白细胞(WBC)计数和血小板(PLT)计数的动态变化情况.结果:以外周血白细胞计数达到4.0～13× 109/L、血小板达计数到50× 109/L为治疗有效,160例患者术后3个月时外周血白细胞治疗有效为151例(94.38％),血小板治疗有效为155例(96.88％),术后6个月时白细胞治疗有效136例(85％),血小板治疗有效125例(78.13％).所有患者术后6个月均未发生严重并发症.结论:PSE联合TACE治疗原发性肝癌合并有脾功亢进患者具有良好的疗效,且安全性较高.

Rationale and Objectives: To assess patient radiation dose reduction and the image quality of a new Xray imaging technology during repetitive transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC).Methods: Fifty HCC patients (36 men; 57 11 years) undergoing repetitive TACE were first randomly assigned to receive a TACE treatment on a reference X-ray system or a low-dose system with advanced real-time image processing. The alternate system was used for a repeated TACE (treatment interval, 0.5-6 months). Fluoroscopy time, number of digital subtraction angiography (DSA), air kerma (AK), and dose area product (DAP) were compared between the two systems and between the two repetitive TACE. Three interventional radiologists independently rated the image quality in blinded offline readings.Results: Fluoroscopy time (8.7 +/- 5.9 minutes vs. 8.7 +/- 7.9 minutes, P =.981), numbers of DSA runs (6 +/- 4 vs. 6 +/- 4, P =.735), and exposure images (173 +/- 86 vs. 168 +/- 91, P =.916) were equivalent between the two systems. No statistical difference in X-ray usage was found between repeated treatments. Compared to the reference system, the technology significantly reduced AK and DAP by 48.6% (0.17 +/- 0.13 Gy vs. 0.41 +/- 0.36 Gy, P <.0001) and 50.3% (77.3 55.2 Gy cm(2) vs. 195.0 +/- 155.5 Gy cm(2), P <.0001), respectively. Image quality was rated comparable between the new system and the reference, with average scores of 3.9 +/- 0.3 versus 4.4 +/- 0.3 in fluoroscopy and 4.5 +/- 0.2 versus 4.3 +/- 0.3 in DSA.Conclusions: Patient radiation exposure can be substantially reduced by a factor of approximately two with the novel X-ray imaging technology while maintaining image quality.

目的:探讨血管成形术治疗下肢动脉硬化闭塞症的临床应用价值.方法:对我院78例下肢动脉硬化闭塞患者的临床资料进行回顾性分析.78例患者(98条血管)术前经CTA诊断后,行腔内血管成形术(PTA)和血管支架植入术治疗,治疗后随访1～18个月,分析踝/肱指数(ABI)、血管内径、皮温及足背动脉搏动的变化.结果:成功完成77例(98.7％)患者、97条(99.0％)患肢的PTA和支架植入术,除1例下肢动脉完全闭塞患者导丝未能成功通过病变导致介入失败外,其余病例经介入治疗后均开通,术中所有病例均未发生血肿、血管壁破裂、穿孔或内支架移位,远端血管血栓栓塞等并发症.术后,患者下肢缺血症状消失或明显减轻,踝/肱指数(ABI)由术前(0.39± 0.23)恢复至(0.86± 0.26),下肢血管内径及足背动脉搏动均明显改善.结论:PTA和血管支架植入术是一种治疗下肢动脉硬化闭塞症安全有效的方法,成功率高,并发症少,再狭窄率低.

Objective: To investigate the effect of the standardized nursing in mini-invasive interventional embolization for acute renal bleeding.Methods: Retrospectively analyzed 38 cases of acute renal bleeding,which bleeding arteries were embolized with gelatin sponge particles,micro spring circles and polyvinyl alcohol(PVA) embolic agents,standardized nursing was carried out before,during and after the intervention.Results: Gross hematuria in all cases was changed to pink in 3 days and completely disappeared in 7 days after interventional embolization,except 2 cases continued for 10 days.Conclusions: Standardized nursing is an important point of minimally invasive embolization in acute kidney bleeding cases,re-bleeding rate after interventional therapy reduced greatly by standardized nursing before,during and after the interventional operations.

99  mTcN-MPO ([99  mTcN(mpo)(PNP5)]+: mpo = 2-mercaptopyridine oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a cationic 99  mTc-nitrido complex, which has favorable biodistribution and myocardial uptake with rapid liver clearance in Sprague Dawley rats. The objective of this study was to compare the biodistribution and pharmacokinetics of 99  mTcN-MPO and 99  mTc-Sestamibi in normal dogs, and to evaluate the potential of 99  mTcN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction.

Objective The purpose of the present study is to compare the pharmacokinetic and biodistribution properties of 99Tcm N-mercaptopyridine-N-oxide (99 Tcm N-MPO) with 99 Tcm-sestamibi (99 Tcm-MIBI) in normal dogs, and to investigate the potential of 99TcmN-MPO as a myocardial perfusion agent in canines with acute myocardial infarction. Methods Twelve healthy mongrel dogs were injected intravenously with 99TcmN-MPO (n = 6) or 99Tcm-MIBI (n = 6). Tracer kinetics in body fluids were determined by collecting blood of 1 ml via a femoral vein catheter at 30 s, 1,2,3,4,5, 10, 20, 30, 40, 60and 90 min post-injection (p. i.). The collected blood samples were weighed and counted for radioactivity in a γ-counter. Anterior and posterior planar γ-camera images were collected at 10, 20, 30, 60, 90, and 120 min after injection, with organ uptake quantified by region-of-interest (ROIs) analysis. For comparison, 99Tcm-MIBI was also evaluated in the same twelve dogs. Canine infarct models were set up by micro-invasive interventional embolization. SPECT images in the canine infarct model were collected 24 hours after myocardial infarction at 30 min and 60 min after the administration of 99Tcm N-MPO (n = 5) or 99Tcm-MIBI (n = 5). Results Both of 99Tcm N-MPO and 99Tcm-M1BI had a rapid blood clearance with less than 50% of initial radioactivity remaining at 1 min [99TcmN-MPO: (35. 77 ± 6. 31)% ID/mg ,99Tcm-MIBI (34. 46 ± 6. 83) % ID/mg] and less than 5% at 30 min p. i. [99Tcm N-MPO(3. 11 ± 1.44) % ID/mg,99Tcm-MIBI (2.93 ±0. 39)% ID/mg] . After injection, 99TcmN-MPO showed significant accumulation in the myocardium and prolonged retention. This rapid liver clearance of 99TcmN-MPO led to favorable heart-to-liver ratios, reaching values of 0. 54 ±0. 06 at 10 min, 1.02 ±0. 06 at 30 min, and 1.38 ±0. 06 at 60 min p. i.In contrast, the heart/liver ratio of 99Tcm-MIBI remained low at all time points (0. 46 ± 0. 03 at 10 min,0. 63 ±0. 03 at 30 min, and 0. 62 ± 0. 12 at 60 min p. i.). SPECT imaging studies in canines with acute myocardial infarction indicated that good visualization of the left ventricular wall and perfusion defects could be achieved at 30 min after administration of 99TcmN-MPO, but not 99Tcm-MIBI. Conclusion The combination of high heart uptake and rapid liver clearance makes 99TcmN-MPO a promising new radiotracer for myocardial perfusion imaging.

Objective: To explore the feasibility of developing precise, low risk, mini-invasive, reproducible technique of AMI on dogs with gelatin sponge by interventional occlusion via femoral artery. Methods: 12 dogs were included in this experiment. After anesthesia and tracheal cannula, a trifle of gelatin sponge was injected into the distal branch of the left anterior descending (LAD) coronary artery through cardiac catheter guided by digital subtraction angiography (DSA). Electrocardiography and blood pressure were monitored during the whole operation. Some enzymatic activities (or the enzyme profile) of the dog blood serum were measured pre and 1, 3, 6, 12, 24 hours after MI by the standard biochemical method. Coronary angiography and Single photon emission computed tomography (SPECT) were performed to identify the acute myocardial infarction. Hematoxylin and Eosin staining (HE) were applied to confirm AMI after the dogs were sacrificed. Results: After interventional occlusion of the distal branch of LAD, 2 dogs were sudden death caused by ventricular fibrillation during the operation. 10 dogs survived 24 h after MI remained alive at 28 days. Electrocardiograph(ECG) revealed abnormal ST segment elevation in leads V 1-V3,Ⅱ,Ⅲ and aVF. The AST,CK,CK-MB,LDH and cTnI activities were increased after AMI. Interruption of the arterial blood stream was affirmed by DSA. Perfusion defects could be achieved at 30 min after administration of 99mTcN-MPO. HE stains proved that AMI had been made successfully. Conclusions: This mini-invasive interventional method to develop the AMI animal model could be applied as a preferred technique in experimental study because of its better trustiness and safeness.