Translational assessment of a DATA-functionalized FAP inhibitor with facile 68Ga-labeling at room temperature
Alondra Escudero-CastellanosJens KurthSurachet ImlimthanElena Arias MenéndezEirinaios PilatisEuy Sung MoonTilman LäppchenHendrik RathkeSarah M. SchwarzenböckBernd J. KrauseFrank RöschAxel RomingerEleni Gourni
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Abstract:
The present study aims at evaluating the preclinical and the clinical performance of [68Ga]Ga-DATA5m.SA.FAPi, which has the advantage to be labeled with gallium-68 at room temperature.[68Ga]Ga-DATA5m.SA.FAPi was assessed in vitro on FAP-expressing stromal cells, followed by biodistribution and in vivo imaging on prostate and glioblastoma xenografts. Moreover, the clinical assessment of [68Ga]Ga-DATA5m.SA.FAPi was conducted on six patients with prostate cancer, aiming on investigating, biodistribution, biokinetics, and determining tumor uptake.[68Ga]Ga-DATA5m.SA.FAPi is quantitatively prepared in an instant kit-type version at room temperature. It demonstrated high stability in human serum, affinity for FAP in the low nanomolar range, and high internalization rate when associated with CAFs. Biodistribution and PET studies in prostate and glioblastoma xenografts revealed high and specific tumor uptake. Elimination of the radiotracer mainly occurred through the urinary tract. The clinical data are in accordance with the preclinical data concerning the organ receiving the highest absorbed dose (urinary bladder wall, heart wall, spleen, and kidneys). Different to the small-animal data, uptake of [68Ga]Ga-DATA5m.SA.FAPi in tumor lesions is rapid and stable and tumor-to-organ and tumor-to-blood uptake ratios are high.The radiochemical, preclinical, and clinical data obtained in this study strongly support further development of [68Ga]Ga-DATA5m.SA.FAPi as a diagnostic tool for FAP imaging.Keywords:
Biodistribution
mTc (CO)3-EC] was prepared and its biodistribution in mice was studied. Biodistribution study revealed that it had pretty high initial kidney uptake and fast renal clearance. It would be helpful for further study of carbonyl technetium core used in the field of kidney imaging agents.
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Objective
To synthesize N- (5-nitroindazole-3-formyl) tyrosine sodium and investigate its hypoxic radiosensitizing effect and biodistribution.
Method
Synthesized the target compound (N- (5-nitroindazole-3-formyl) tyrosine sodium) using condensing agents, and investigated its radiosensitization under hypoxia using H22 xenograft models and its biodistribution using radioactive iodine labeling.
Results
The synthesis and structure of the target compound were confirmed. Xenograft models showed that it had a certain radiosensitizing activity and the mean value of sensitization enhancement ratio was 1.5. Biodistribution experiment revealed that it had a good distribution manner, the distribution ratios of tumor to the nervous system and muscle were both greater than 5.
Conclusion
N- (5-nitroindazole-3-formyl) tyrosine sodium had good radiosensitizing activity and biodistribution manner, and it was worthy of further study.
Key words:
N- (5-nitroindazole-3-formyl) tyrosine sodium; Neoplasms; hypoxic radiosensitization; biodistribution
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Radiosensitizer
Sodium pump
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金 nanoparticles (AuNPs ) 的 biodistribution 是仔细与毒物学的效果有关并且因为他们的潜在的申请，担心大。与为液体运输的新奇解剖、组织学的结构的发现，然而，内在的机制包含了在在里面 AuNPs 的 vivo 运输和 biodistribution 要求进一步深入的调查。在当前的学习，在腱，容器，和神经纤维的一个焦点的点可以最佳地与另外的遥远的结缔组织连接的地方，我们在跗骨的隧道在 intervaginal 空间注射(ISI ) 以后在老鼠调查了 10-nm AuNPs 的 biodistribution。AuNPs 的静脉内的注射(IVI ) 用作控制。血和机关与诱导地联合的血浆团 spectrometry (ICPMS ) 为 Au 分发的定量分析在注射以后在 5， 15，和 30 min 并且在 1， 4， 12，和 24 h 被收集。IVI 和 ISI 产出显著地不同的结果：在在 ISI 以后的血的 AuNP 内容在 IVI 以后是比那低得多的；在肺，心，和肠是类似的；并且在皮和肌肉是更高的。这些调查结果被 AuNP 内容和相对机关 AuNP 分发比例的比率支持。我们表明的结果一快，直接并且发行量无关的 AuNP 器官运输小径，它可以改进我们生理、病理学的 biodistribution 的理解在生物系统处理。而且，这些结果提供新奇卓见进在里面 vivo 运输和 AuNPs 的 biodistribution，它可以导致新奇、有效治疗学并且管理策略。
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HEDTMP (N(2hydroxyethyl) ethlenediamine1,1,2tri(methylene phosphonic acid)) is labeled with 99Tcm. The stability, rabbit bone imaging and mice biodistribution of 99TcmHEDTMP are investigated. The stability studies show that99TcmHEDTMP is stable in 5 h. The biodistribution indicate 99TcmHEDTMP is mainly concentrated on animal skeleton and the uptake of nontarget tissue is low. The results show that 99TcmHEDTMP is a potential promising bone imaging agent.
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Control of the biodistribution of radiolabeled peptides has proven to be a major challenge in their application as imaging agents for positron emission tomography (PET). Modification of peptide hydrophilicity in order to increase renal clearance has been a common endeavor to improve overall biodistribution. Herein, we examine the effect of site-specific sulfonation of tyrosine moieties in cyclic(RGDyK) peptides as a means to enhance their hydrophilicity and improve their biodistribution. The novel sulfonated cyclic(RGDyK) peptides were conjugated directly to 4-nitrophenyl 2-[18F]fluoropropionate, and the biodistribution of the radiolabeled peptides was compared with that of their nonsulfonated, clinically relevant counterparts, [18F]GalactoRGD and [18F]FPPRGD2. Site-specific sulfonation of the tyrosine residues was shown to increase hydrophilicity and improve biodistribution of the RGD peptides, despite contributing just 79 Da toward the MW, compared with 189 Da for both the "Galacto" and mini-PEG moieties, suggesting this may be a broadly applicable approach to enhancing biodistribution of radiolabeled peptides.
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PURPOSE: People consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate (99mTc-GH) and radiolabeling of blood components. METHODS: GH was labeled with 99mTc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl2 and 99m Tc. RESULTS: Radiochemical yield of 99mTc-GH is 98.46±1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. CONCLUSIONS: Although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine.
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Abstract Prostate stromal cells may play binary roles in the process of prostate cancer development. Being the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. On the other hand, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal cells. The specimens were from three prostate cancer patients who underwent radical prostatectomy in the Department of Urology, Emory University School of Medicine. From each prostate, a cube of prostate tissue was dissected from a histologically normal region distal to the tumor, and another cube was dissected from a cancer-affected zone. Live cells in single cell preparation were cultured in low density for isolation of stromal clones. In contrast to the LNCaP prostate cancer cells, the isolated prostate stromal clones exhibited large fibroblastic morphology with slow growth rate. Growth and survival of the stromal clones were not affected by androgens and were highly resistant to serum starvation. In contrast to the normal counterparts, the cancer-associated stromal clones exhibited differentiated survival ability, as determined by colony formation assay following serum starvation. In direct co-culture, the prostate stromal cells inhibited growth of the LNCaP cells and made the production of Prostate Specific Antigen (PSA) less sensitive to androgen deprivation. Importantly in co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. The surviving LNCaP clones showed features of androgen-independent PSA expression similar to the lineage-related androgen-independent C4-2 cells, suggesting that cancer cells acquired increased malignancy through interaction with the stromal cells. The results from this study indicate that matched stromal cell pairs may serve as models for comparative analysis of molecular changes in the tumor microenvironment. These cells can also be used in co-culture with prostate cancer cells to simulate cancer-stromal interaction in the tumor microenvironment in order to define the role of prostate stromal cells in prostate cancer progression and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 561.
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Biodistribution of nanoparticles (NPs) depends on properties such as size, shape, charge, and surface modification, which can affect particle interaction with cells and serum proteins. This chapter highlights the impact of the mechanisms affecting biodistribution, such as physicochemical properties, administration route, dosing and coating, on behaviors of NPs in systemic circulation, effects of mononuclear phagocytotic systems and cellular interactions on the targeted tissue. Particle size is a key parameter in the biodistribution of NPs, which can be designed to precise dimensions and high monodispersity to attain therapeutic efficacy. The surface charge and hydrophobicity can dramatically affect opsonization, phagocytosis, blood circulation and biodistribution of NPs. One of the factors affecting the biodistribution of polymeric, polysaccharide and metallic NPs is surface coating. Opsonization of NPs has one of the most important effects on biodistribution and organ accumulation. Opsonization is a defense mechanism that the body shows against foreign material.
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