DISTRIBUTION AND ELIMINATION OF PHOTOFRIN II IN MICE

The distribution and elimination of [14C]PII, the radioisotopically-labeled equivalent of the mixture of porphyrins known as Photofrin II used in the photodynamic treatment of solid tumors, were determined in tumor-free and SMT-F tumor-bearing DBA/2 Ha-DD mice. Following i.p. injection, drug was absorbed from the peritoneum with a half-life of about 1 h; elimination from plasma was rapid, declining about 1.4 logs in concentration over 48 h following i.v. administration. However, some [14C]-activity was still detectable after 75 days. Normal tissues take up the drug within about 7.5 h after administration, with peak concentrations distributed as follows: liver, adrenal gland, urinary bladder greater than pancreas, kidney, spleen greater than stomach, bone, lung, heart greater than muscle much greater than brain. Only skeletal muscle, brain, and skin located contralaterally to subcutaneously implanted SMT-F tumors had peak [14C]-activities lower than tumor tissue; skin overlying SMT-F tumors showed concentrations not significantly different (P greater than 0.3) from tumor. After 75 days all tissues examined retained some fraction of [14C]-activity, ranging from 16% for kidney to 61% for spleen, of the initial peak tissue levels. The primary route of elimination of Photofrin II was through the bile-gut pathway, with greater than 59% of the administered [14C]-activity recovered in the feces, and only about 6% in the urine, over 192 h. HPLC analyses of fecal extracts showed that mostly monomeric and other low molecular weight porphyrin components of Photofrin II were eliminated. The higher molecular weight oligomeric fractions of Photofrin II were retained in liver and spleen up to 14 days after injection.     

Biodistribution and Pharmacokinetic Studies of a Porphyrin Dimer Photosensitizer (Oxdime) by Fluorescence Imaging and Spectroscopy in Mice Bearing Xenograft Tumors

Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne‐linked conjugated porphyrin dimer (Oxdime) designed to have high near‐infrared (NIR) 2‐photon absorption cross‐section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16‐F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organs ex vivo at different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5–10 times higher than in other tissues. The fluorescence signal peaked at 3–12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment.     

Biodistribution of ultra small superparamagnetic iron oxide nanoparticles in BALB mice

Recently ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) have been widely used for medical applications. One of their important applications is using these particles as MRI contrast agent. While various research works have been done about MRI application of USPIOs, there is limited research about their uptakes in various organs. The aim of this study was to evaluate the biodistribution of dextran coated iron oxide NPs labelled with ^99mTc in various organs via intravenous injection in Balb/c mice. The magnetite NPs were dispersed in phosphate buffered saline and SnCl₂ which was used as a reduction reagent. Subsequently, the radioisotope ^99mTc was mixed directly into the reaction solution. The labeling efficiency of USPIOs labeled with ^99mTc, was above 99 %. Sixty mice were sacrificed at 12 different time points (From 1 min to 48 h post injections; five mice at each time). The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The biodistribution of ^99mTc-USPIO in Balb/c mice showed dramatic uptake in reticuloendothelial system. Accordingly, about 75 percent of injected dose was found in spleen and liver at 15 min post injection. More than 24 % of the NPs remain in liver after 48 h post-injection and their clearance is so fast in other organs. The results suggest that USPIOs as characterized in our study can be potentially used as contrast agent in MR Imaging, distributing reticuloendothelial system specially spleen and liver.     

WST11, a novel water-soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model

WST11 is a novel negatively charged water-soluble palladium-bacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t1/2=1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t1/2=7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t1/2=20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm2. These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates.     

Biological activities of phthalocyanines. XII: Synthesis tumor uptake and biodistribution of 14C-labeled disulfonated and trisulfonated gallium phthalocyanine in C3H mice

The biodistribution and metabolism of 14C-labeled disulfonated and trisulfonated gallium phthalocyanine (Ga-PcS) was studied in radiation-induced fibrosarcoma tumor-bearing C3H mice. The [14C]Ga-PcS compounds were prepared via the condensation of [14C]phthalic acid and sulfophthalic acid in the presence of gallium chloride and characterized by their spectroscopic and chromatographic properties. The tissue concentrations of the dyes was measured by scintillation counting of the 14C and by extraction and fluorescence measurements. Elevated dye levels were found in the liver, lungs, kidneys and spleen as well as in the tumor. Lower sulfonation of Ga-PcS favored liver and spleen uptake whereas higher dye sulfonation resulted in greater kidney uptake. Both dyes showed high tumor uptake with peak concentrations exceeding those of most tissues except for the liver in the case of Ga-PcS2. The highest tumor uptake was observed with Ga-PcS3. Both dyes were slowly excreted from the body. The liver-feces pathway was favored in the case of Ga-PcS2 with high activities persisting in the liver, even after 21 days. The Ga-PcS3 was preferentially excreted via the kidney-urine pathway. High performance liquid chromatography analysis of the liver and tumor extracts of [14C]Ga-PcS3-treated animals did not reveal desulfonation of the dye. However, urine analysis showed the presence of radioactive metabolites lacking the characteristic phthalocyanine absorption.     

Pharmacokinetics, tissue distribution and photodynamic therapy efficacy of liposomal-delivered hypocrellin A, a potential photosensitizer for tumor therapy

Hypocrellin A, from Hypocrella bambusae, is a novel photosensitizer of high singlet oxygen quantum yield for photodynamic therapy (PDT). Tissue distributions were studied in tumor-bearing mice as a function of time following administration. The tumor model was S-180 sarcoma transplanted into one hind leg of male Kunming mice; hypocrellin A (HA) was delivered to the mice by intravenous injection of 5 mg/kg of body weight as a suspension either as a unilamellar liposome or in dimethyl sulfoxide (DMSO)-solubilized saline. The HA was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin. Quantitation was performed by a high-performance liquid chromatographic technique with detection that utilizes the native fluorescence of HA. Independent of the delivery system, the dye was retained in tumors at higher concentrations than in normal tissues, except for kidney, liver, lung and spleen. The dye retention in tumors was high and was vehicle dependent. For the liposomal system, the maximal accumulation in tumor and maximal ratios of dye in tumor versus peritumoral muscle and skin occurred 12 h postinjection; for the DMSO saline system, the maximal ratio occurred earlier, 6 h postadministration. Liposomal delivery improved the selective accumulation of the dye in tumor with higher maximal levels in tumor and higher ratios of tumor-to-muscle and tumor-to-skin. Levels of dye were very low or not detectable in the brain. The PDT efficacy of HA in the liposome and DMSO saline systems was determined by evaluating the tumor volume regression percent. The PDT efficacy of HA in liposomes was highest when light treatment was performed at 12 h postinjection, consistent with the highest retention of HA in tumors. Similarly, the maximal PDT efficacy in DMSO saline was attained at 6 h postinjection, the highest HA retention point in tumor. Moreover, the peak PDT efficacy of HA in liposomes was much higher than that of HA in DMSO saline and even hematoporphyrin monomethylether.     

PHARMACOKINETIC AND TISSUE DISTRIBUTION STUDIES OF THE PHOTOSENSITIZER bis(DI-ISOBUTYLOCTADECYLSILOXY)SILICON 2,3-NAPHTHALOCYANINE (isoBOSINC) IN NORMAL AND TUMOR-BEARING RATS

Abstract Bis (di-isobutyl octadecylsiloxy)silicon 2,3-naphthalocyanine ( iso BOSINC) is a representative of a group of naphthalocyanine derivatives with spectral and photophysical properties that make them attractive candidates for photodynamic therapy (PDT). Tissue distributions were studied in normal and in tumor-bearing rats as a function of time following intravenous injection of iso BOSINC as a suspension in 10% Tween 80 in saline. The dose studied was 0.25 mg/kg of body weight. The compound iso BOSINC was isolated from several tissues and organs, as well as tumors and peritumoral muscles and skin, and quantitated by a high-performance liquid chromatographic technique. The tumor model, an N -(4-[5-nitro-2-furyl)-2-thiazolyl)formamide (FANFT)-induced urothelial cell carcinoma, was transplanted into the hind legs of Fischer 344 rats. The dye was retained in tumors at higher concentrations than in all tissues and organs examined, except for spleen and liver. The highest concentration ratio of dye in tumor versus peritumoral muscle (24.5) occurred 9 h after injection. Serum clearance of iso BOSINC showed similar kinetic behavior for both groups of rats, with a t_1/2 of elimination of ∼ 10 h. At 7 and 14 days postinjection, the levels of dye found in testes were generally higher than in most other tissues, except spleen and liver. Concentrations of iso BOSINC were either very low or not detectable in rat brain. Trace amounts of the dye were excreted in the urine, and by day 14 approximately 17% of the dose was accounted for in the feces. The significant levels of the drug in tumors, as well as the excellent ratios of tumor-to-muscle concentration observed, have promising implications for PDT of tumors.     

MODIFIED POLYVINYL ALCOHOL-BENZOPORPHYRIN DERIVATIVE CONJUGATES AS PHOTOTOXIC AGENTS

Abstract— Photosensitizing and biodistribution characteristics of a photosensitizer(benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight=10000) were tested in vitro and in vivo . Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated ³H-BPD and 3 h later light activation of tumor cells was carrie out in vitro . Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and ³H-BPD either free or conjugated to M-PVA. The result of there these studies showed that the conjugatin of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing avtivity of the photosensitizer molecules and at the same time gained new charcteristics, advantageous from photodynamic treatment, especially in vivo . In vitro M-PVA-BPD conjugates were at least as efficient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparabel to free BPD, the conjugate(1:25) reached slightly higher leves in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD. Although the level of M-PVA-BPD in tumor tissue was lower than tht of free BPD under comparable conditions, the conjugate was bound more tightly to the tumor cells and effected higher tumor cell kill when activated by light     

Doxorubicin-loaded boron-rich polymer nanoparticles for orthotopically implanted liver tumor treatment

The in vivo behaviors of doxorubicin(DOX)-loaded dextran-poly(3-acrylamidophenylboronic acid)(DextranPAPBA) nanoparticles(NPs) were studied.The DOX-loaded NPs had a narrowly distributed diameter of ca.74 nm and mainly accumulated in liver of tumor-bearing mice after intravenous injection as demonstrated by in vivo real-time near infrared fluorescent imaging.The DOX contents in various tissues were quantified and consisted well with the results of fluorescent imaging.The biodistribution pattern of DOX-loaded NPs encourages us to investigate their liver tumor treatment by using an orthotopically implanted liver tumor model,revealing that the DOX-loaded NPs formulation had better antitumor effect than free DOX.     

Preparation and biological evaluation of radiogallium labeled glucagon for SPECT imaging

In this work, recently prepared ⁶⁷Ga-labeled glucagon (⁶⁷Ga-DTPA-GCG) for imaging studies (radiochemical purity >94%; HPLC, S.A. 296–370 GBq/mM) was used in biological studies. The wild-type rat biodistribution results, 2 h post injection, demonstrated high tissue:muscle ratios for target tissues (liver, kidney, heart, spleen, fat intestine stomach and pancreas), 234, 18.45, 7.12, 1.75, 128.7, 4.9, 6.3 and 1.11, respectively. The tracer binding capacity using freshly prepared rat brain homogenate demonstrated significant specific binding of the tracer to neuronal GCG receptors (⁶⁷Ga-DTPA-GCG/⁶⁷Ga:3 and ⁶⁷Ga-DTPA-GCG/⁶⁷GaDTPA:2.2 at 90 min). SPECT images also demonstrated target specific binding of the tracer at 4 h. The data suggests the tracer is accumulated in GCGR rich tissues 2–4 h post injection, suggesting potentials of the tracer for future imaging studies in glocagonoma models.     

LIPOSOMAL DELIVERY OF A PHOTOSENSITIZER, BENZOPORPHYRIN DERIVATIVE MONOACID RING A (BPD), TO TUMOR TISSUE IN A MOUSE TUMOR MODEL

Abstract— Biodistribution studies were carried out on ¹⁴C-labeled benzoporphyrin derivative monoacid ring A (BPD), which had been formulated as a unilamellar liposome or taken from a stock solution in dimethyl sulfoxide diluted into phosphate-buffered saline immediately before intravenous injection into DBA/2 mice. By and large the general distribution of BPD to various organs and tissues was comparable for both formulations. It was noted, however, that liposomal material appeared to enter tissues more rapidly and to be cleared more rapidly, as demonstrated by shorter half-lives for a number of tissues including skin, lung and fat, and generally lower levels in most tissues 24 h following administration. Accumulation in tumor tissue was slightly higher with liposomal BPD, and clearance rates for this tissue were equivalent (half-lives 16.1 h for liposomal BPD and 16.9 h for aqueous BPD). When the two preparations were tested in a bioassay in tumor-bearing mice, photodynamic therapy (PDT) with liposomal BPD proved to be superior to the aqueous preparation when PDT was administered 3 h following intravenous administration of BPD. Plasma distribution studies in vitro demonstrated that 91.1 ± 0.3% of the liposomal BPD distributed to the lipoprotein fraction within the first hour of mixing, whereas only 49.1 ± 2.6% of nonliposomal BPD was associated with lipoprotein under the same conditions. Furthermore, while lipoprotein-associated liposomal BPD distributed evenly between all three types of lipoprotein (high, low and very low density), a majority of nonliposomal BPD associated with the high-density lipoprotein fraction.     

Liposomes prepared from synthetic amphiphiles. II. Their interaction with Ehrlich ascites tumor cells and tissue distribution in Ehrlich solid tumor-bearing mice

The interaction of 99mTc-labeled liposomes prepared from synthetic amphiphiles containing amino acid residues with Ehrlich ascites tumor cells in vitro and their tissue distributions in Ehrlich solid tumor-bearing mice were investigated. The amphiphiles used were N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide N+C5Ala2C12), N,N-didodecyl-N alpha-(6-[dimethyl(2-carboxyethyl)ammonio]hexanoyl)-L- alaninamide bromide (CAC2N+C5Ala2C12) and S-[1-carboxy-2- ([2,3-bis(hexadecyloxy)propoxy]carbonyl)ethyl]homocysteine (HcyM-G2C1 6). Most of the radioactivity of N+C5Ala2C12 and CAC2N+C5Ala2C12 liposomes was firmly bound to Ehrlich ascites tumor cells in vitro. On the other hand, the accumulation of three 99mTc-labeled liposomes in the tumor of Ehrlich solid tumor-bearing mice was low (about 1% dose per gram of tissue), and most of the liposomes were taken up highly in the liver and spleen of the tumor-bearing mice. However, the radioactivity of the liposomes in the tumor, especially that of N+C5Ala2C12 and CAC2N+C5Ala2C12 liposomes, decreased more slowly with time than in the liver in up to 24 h after injection, suggesting that these liposomes were hard to separate from the tumor cells.     

Biodistribution assessment of a lutetium(III) texaphyrin analogue in tumor-bearing mice using NIR Fourier-transform Raman spectroscopy

The use of near-infrared (NIR)-excited Fourier-transform (FT) Raman spectroscopy as a technique for evaluating the extent of photosensitizer localization in tumor (human pancreatic adenocarcinomas)-bearing mice has been tested using lutetium(III) texaphyrin analogue Lu-T2B2Tex. The complex was injected subcutaneously in the form of three injections given during the course of 3 days. The kinetics of biodistribution were then followed over a time scale of 1-6 days. The NIR-FT-Raman spectra of tissue samples obtained from the xenographic tumor, muscle, heart, brain, liver, spleen, kidney and blood were recorded and used to identify the presence of Lu-T2B2Tex in these tissues. Five Raman sensitizer markers were used to estimate the relative content of Lu-T2B2Tex in tumor at various postinjection times. UV-Visible (Vis) absorption spectroscopic detection of this sensitizer in tissue extracts was applied as a conventional method. Both spectroscopic methods were in good agreement with each other and confirm that Lu-T2B2Tex localizes well in tumor tissue. Maximal drug content was observed 3 days after the final injection. This time delay seems to be optimal for tumor irradiation in photodynamic therapy.     

The case for fractional solubility profiles

This work reports the synthesis, radiolabeling and preliminary biodistribution results in tumor-bearing mice of [^99mTc(CO)₃(PA-TZ-CHC)]⁺. The novel colchicine (CHC) ligand was successfully synthesized via “click” reaction. Radiolabeling was performed in high yield with [^99mTc(CO)₃]⁺ core to get [^99mTc(CO)₃(PA-TZ-CHC)]⁺, which was hydrophilic and cationic, and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [^99mTc(CO)₃(PA-TZ-CHC)]⁺ accumulated in the tumor with good uptake while comparatively low retention. The clearance of the ^99mTc-complex from normal organs was fast, resulting in increasing tumor/blood and tumor/muscle ratios. The promising results in preliminary biodistribution studies warrant further research to improve tumor targeting efficacy and pharmacokinetic profile of radiolabeled CHC derivative by structural modification.     

叶酸高分子纳米胶束在小鼠体内的靶向分布

合成了带有叶酸靶向和荧光染料的聚合物FA-PEG-PLA和mPEG-b-P（LA-co-MHC／NIR）,通过混合胶束的方法制备近红外染料胶束P（NIR）（含染料NIR6％）,叶酸胶束FA-P（NIR）1（含染料NIR5．4％,叶酸LFA0．5％）和叶酸胶束FA-P（NIR）2（含染料NIR4．8％,叶酸FA0．9％）;建立了H22肝癌小鼠模型,考察了高分子纳米胶束及叶酸靶向纳米胶束在H22肝癌小鼠体内分布．结果表明,高分子纳米胶束及叶酸靶向纳米胶束在小鼠体内分布都具有时间相关性,无叶酸配体的高分子纳米胶束在尾静脉注射24h后在肿瘤部位有少量聚集,大部分胶束在肝部聚集,30h内大部分已被排泄系统排出体外;含有叶酸配体的纳米胶束在尾静脉注射后6-30h内在肿瘤部位有明显的聚集,其中,FA-P（NIR）1胶束在肿瘤和肝部位的聚集相当,FA-P（NIR）2胶束在静脉注射24h后在肿瘤聚集明显高于肝部．带有叶酸配体的高分子纳米胶束相对于不带叶酸配体的纳米胶束在小鼠肿瘤部位具有明显的聚集,并且随着叶酸含量的增大,聚集效果更明显．     

潜在的新型肿瘤显像剂99mTc-MAG3-GGCNGRC的合成及生物分布

为测评带有NGR基序的小分子多肽的99mTc配合物作为新型肿瘤显像剂的可能性,合成了带双功能螯合剂MAG3的环肽并进行了动物体内分布实验.直链短肽GGCNGRC环化为99mTc-MAG3-GGCNGRC,再与苯甲酰基保护的MAG3的N-羟基琥珀酰亚胺活泼酯偶联,生成Bz-MAG3-GGCNGRC.后者通过氧化-配体交换反应生成9mTc-MAG3-GGCNGRC,其放射化学纯度>90%,在血清和生理盐水中具有较好的稳定性.在正常小鼠和荷瘤裸鼠体内的生物分布表明,此类型小肽通过泌尿系统和肝胆系统代谢.荷直肠癌CL-187的裸鼠模型体内分布显示,注射后3h后,99mTc-MAG3-GGCNGRC,在肿瘤中有一定的特异性摄取,可能是由于NGR基序的亲新生血管所致.带有NGR基序的小分子多肽是一类很有发展潜力的新型肿瘤显像剂.     

Application of INAA to the build-up and clearance of gold nanoshells in clinical studies in mice

Clinical studies have been carried out for detailed measurements of the build-up and clearance of engineered gold nanoshell in the tissues of dosed mice. These optically tunable nanoshells are under consideration for a new therapy for tumors. The proposed therapy would involve the injection of the nanoshells and their preferential accumulation in tumor sites. This will be followed by irradiation with a monochromatic near infrared laser, which will induce cellular hyperthermia, thereby eradicating the tumor. Neutron activation analysis has been used for the detection and quantitation of gold, and therefore, the nanoshells, in dosing materials, blood, bones and other tissues as well as tumors at varioius sacrifice times following dosing. Feasibility studies have shown instrumental neutron activation analysis to be uniquely suited for detection of the gold nanoshells over a wide dynamic range. This allows for the study of high concentrations of gold in tissues which scavenge the shells from the blood (liver, spleen, kidney) as well as for much lower concentrations in those which do not (muscle, brain). In particular, the tissues from animals sacrificed after the longest post dose delay (28 days) and the control animals required experimental optimization to ensure the lowest possible determination limits. The mass of gold in the tissue samples ranged from our determination limit (about 70 pg) to a few micrograms.     

Preliminary Study of a 1,5-Benzodiazepine-Derivative Labelled with Indium-111 for CCK-2 Receptor Targeting

The cholecystokinin-2 receptor (CCK-2R) is overexpressed in several human cancers but displays limited expression in normal tissues. For this reason, it is a suitable target for developing specific radiotracers. In this study, a nastorazepide-based ligand functionalized with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator (IP-001) was synthesized and labelled with indium-111. The radiolabeling process yielded >95% with a molar activity of 10 MBq/nmol and a radiochemical purity of >98%. Stability studies have shown a remarkable resistance to degradation (>93%) within 120 h of incubation in human blood. The in vitro uptake of [¹¹¹In]In-IP-001 was assessed for up to 24 h on a high CCK-2R-expressing tumor cell line (A549) showing maximal accumulation after 4 h of incubation. Biodistribution and single photon emission tomography (SPECT)/CT imaging were evaluated on BALB/c nude mice bearing A549 xenograft tumors. Implanted tumors could be clearly visualized after only 4 h post injection (2.36 ± 0.26% ID/cc), although a high amount of radiotracer was also found in the liver, kidneys, and spleen (8.25 ± 2.21%, 6.99 ± 0.97%, and 3.88 ± 0.36% ID/cc, respectively). Clearance was slow by both hepatobiliary and renal excretion. Tumor retention persisted for up to 24 h, with the tumor to organs ratio increasing over-time and ending with a tumor uptake (1.52 ± 0.71% ID/cc) comparable to liver and kidneys.     

Renal‐clearable Molecular Semiconductor for Second Near‐Infrared Fluorescence Imaging of Kidney Dysfunction

Real‐time imaging of kidney function is important to assess the nephrotoxicity of drugs and monitor the progression of renal diseases; however, it remains challenging because of the lack of optical agents with high renal clearance and high signal‐to‐background ratio (SBR). Herein, a second near‐infrared (NIR‐II) fluorescent molecular semiconductor (CDIR2) is synthesized for real‐time imaging of kidney dysfunction in living mice. CDIR2 not only has a high renal clearance efficiency (≈90 % injection dosage at 24 h post‐injection), but also solely undergoes glomerular filtration into urine without being reabsorbed and secreted in renal tubules. Such a unidirectional renal clearance pathway of CDIR2 permits real‐time monitoring of kidney dysfunction in living mice upon nephrotoxic exposure. Thus, this study not only introduces a molecular renal probe but also provides useful molecular guidelines to increase the renal clearance efficiency of NIR‐II fluorescent agents.     

Kinetic distribution of Cu,Se, and Zn in mice during ascites tumor-bearing period

The kinetic distribution of⁶⁴Cu,⁷⁵Se, and^69mZn radioactive tracers were determined in tissues of mice bearing ascites tumors and healthy ones. The HPGe gamma-ray spectrometric detection system was used for radionuclide analysis in tissues which were sampled at various periods after tracer injection during ascitic tumor growth. Significantly different distribution of⁶⁴Cu,⁷⁵Se, and^69mZn were found in colon, small intestine, and liver of tumor-bearing mice. There was a dcerease of⁷⁵Se in ascites and blood of tumor-bearing mice. The⁶⁴Cu and^69mZn concentration varied significantly in kidneys, and a similar effect was observed in the spleen for⁶⁴Cu, too. A distinct variation of tracer distribution is also found at different stages after treatment. The results are discussed within the context of a correlation between elemental concentration and tumor-growth.