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Liposome in delivering radionuclide for cancer therapy has been expansively studied; however, liposome itself can be deliberately entrapped and destroyed by the reticuloendothelial system, causing an insufficiency of the drug delivery, which in turn would restrict the effectiveness of the drug. In this study, mice with subcutaneous implantation of C26 murine colon cancer received an experimental treatment regimen in which mice took delivery of PEGylated liposomal doxorubicin (LipoDox) first, after a three-day interval, of Rhenium-188 encapsulated into PEGylated liposome ((188)Re-Liposome) subsequently and by which suppressed the functioning of reticuloendothelial system for the short term. The data showed that based upon the biodistribution assay and the evaluation of the therapeutic efficacy, (188)Re-Liposome was more sufficiently delivered to tumor sites in mice with this treatment regimen than mice without the regimen, and that cancer mortalities in mice with the treatment regimen were much lower than the mortalities in mice without the regimen. Taken together, a new strategy proposed in this study significantly improved both the (188)Re-Liposome delivery and the effectiveness of (188)Re-Liposome, suggesting that the strategy can be an ideal treatment for cancer.

PEGylated liposomes are important drug carriers for nanomedicine cancer therapy. PEGylated liposomes can encapsulate radio- and chemo-drugs and passively target tumor sites via enhanced permeability and retention effect. This study estimated the pharmacokinetics and dosimetry after administration of radio-chemotherapeutics ((111)In-labeled vinorelbine [VNB]-encapsulated liposomes, InVNBL, and (188)Re-labeled doxorubicin [DXR]-encapsulated liposomes, ReDXRL) for radionuclide therapy in two colon carcinoma-bearing mouse models. A C26 colon carcinoma tumor/ascites mouse model and a subcutaneous solid tumor-bearing mouse model were employed. Biodistribution studies of InVNBL and ReDXRL after intraperitoneal administration in tumor/ascites-bearing mice (protocol A) and intravenous administration in subcutaneous solid tumor-bearing mice (protocol B) were performed. The radiation dose to normal tissues and tumors were calculated based on the results of distribution studies in mice, using the OLINDA/EXM program. The cumulated activities in most organs after administration of InVNBL in either the tumor/ascites-bearing mice (protocol A) or the subcutaneous solid tumor-bearing mice (protocol B) were higher than those of ReDXRL. Higher tumor-to-normal-tissues absorption dose ratios (T/NTs) were observed after administration of InVNBL than those of ReDXRL for protocol A. The T/NTs for the liver, spleen, and red marrow after injection of InVNBL for protocol B were similar to those of ReDXRL. The critical organ was found to be red marrow, and thus the red marrow absorption dose defined the recommended maximum administration activity of these liposomal drugs. Characterization of pharmacokinetics and dosimetry is needed to select the appropriate radiotherapeutics for specific tumor treatment applications. The results suggest that InVNBL is a promising therapeutic agent, which is as good as ReDXRL, in two mouse tumor models.

Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of 188 Re- N , N -bis (2-mercaptoethyl)- N ′, N ′-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ( 188 Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of 188 Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of 188 Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin–eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of 188 Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of 188 Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of 188 Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of 188 Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of 188 Re-liposome and the synergistic effect of the combination radiochemotherapeutics of 188 Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of nanoliposome radiochemotherapeutics for adjuvant cancer treatment on oncology applications.

Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and (111)In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID mice to study the treatments with 6% polyethylene glycol (PEG) of (111)In-NanoX/VNB-liposomes. In vivo tumor growth tracing and BLI showed that tumor volume could be completely inhibited by the combination therapy with (111)In-VNB-liposomes and by chemotherapy with NanoX/VNB-liposomes (i.e., without Indium-111) (P

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications through passive targeting tumor sites by enhanced permeability and retention effect. Radiolabeled liposomes have potential applications in radiotherapy and diagnostic imaging. The purpose of this study was to investigate the biodistribution, pharmacokinetics and imaging of nanotargeted (188)Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomes (RBLPL) and unencapsulated (188)Re-BMEDA after intraperitoneal (ip) injection in a C26 colon carcinoma ascites mouse model. The nanopegylated liposomes were labeled with (188)Re-BMEDA. The labeling efficiency of RBLPL was 82.3+/-4.5%. In vitro stability of RBLPL in normal saline at room temperature and in rat plasma at 37 degrees C for 72 h was 92.01+/-1.31% and 82.4+/-1.64%, respectively. The biodistribution studies indicated that the radioactivity in ascites was 69.96+/-14.08 percentage injected dose per gram (% ID/g) at 1h to 5.99+/-1.97% ID/g at 48 h after ip administration of RBLPL. The levels of radioactivity in tumor were progressive accumulation to a maximum of 6.57+/-1.7% ID/g at 24 h. The radioactivity of (188)Re-BMEDA in ascites reached the maximum level of 54.89+/-5.91% ID/g at 1 h and declined rapidly with time. Pharmacokinetic studies revealed that the terminal half-life, total body clearance and area under the curve of RBLPL were 5.3-, 9.5- and 9.4-fold higher than that of (188)Re-BMEDA in blood, respectively. These results suggested that the long circulation, bioavailability and localization of RBLPL in tumor and ascites sites, which also demonstrate that the ip administration of RBLPL is a potential multifunctional nanoradiotherapeutics and imaging agents on a C26 colon carcinoma ascites mouse model.

A radiopharmaceutical, 123 I-labeled 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine ([ 123 I]ADAM), has been developed recently for evaluation of how serotonin transporters (SERT) function in the brain. However, the detailed biodistribution and specific binding in certain brain areas are not well investigated. In this study, both phosphor plate imaging and microautoradiography were applied to explore the binding characteristics of [ 123 I]ADAM in SERT neurons. The effect of two psychotropics and one narcotic on the binding of [ 123 I]ADAM to SERT was also studied. Fluoxetine and desipramine, both are psychotropics and specific SERT ligands and decreased the affinity of [ 123 I]ADAM, while p-chloroamphetamine (PCA), a narcotic, destroyed most of serotonergic neurons, as well as reducing the concentration of serotonin and the number of SERT in the brain as shown by the biodistribution of [ 123 I]ADAM. Significant and selective accumulation of [ 123 I]ADAM in the areas from midbrain to brain stem in normal mice with maximum target-to-background ratio was found at 90 minutes postinjection. A rapid clearance of [ 131 I]ADAM at 120 minutes postinjection was found in the CA1, CA3 and ThN brain areas. In addition, the inhibition effect on binding ability of [ 123 I]ADAM to SERT by the psychotropics and the narcotic was found to have the order of: PCA > fluoxetine > desipramine.

This study aims to investigate the relationship between the determination of dopamine level by high performance liquid chromatography (HPLC) with electrochemical detection (ECD) and the detection of dopamine transporter (DAT) counts using autoradiography with DAT image agent [99mTc]TRODAT-1. For striatal lesions, pretreatment of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle shows that autoradiogaphic labeling of striatum region is reduced to near-background level. Using HPLC with ECD, unilateral 6-OHDA treatment is associated with significant (p < 0. 0002) reductions of dopamine levels. For the striatum of the 6-OHDA-lesioned side, dopamine content and DAT counts are reduced to 97% and 90%, respectively. Thus, our observation indicates a potential of using [99mTc]TRODAT-1 for the evaluation of animal DAT.

Rhenium-188 microsphere is a relatively new radiation synovectomy agent developed for the treatment of rheumatoid arthritis. It has been shown that the levels of unwanted extra-articular radiation are negligible with this agent. A histologic study was conducted to assess the effect of radiation synovectomy on synovium and articular cartilage after intra-articular injection of various doses of Re-188 microspheres into the knee joints of rabbits. Intra-articular injection of Re-188 microspheres into rabbit knee joints resulted in mild reactive inflammation and thrombotic occlusion of vessels which subsided rapidly. Sclerosis of subsynovium could be seen 12 weeks after injection. No evidence of damage to articular cartilage was noted. There was no significant difference in the articular pattern after injection of 0.3 or 0.6 mCi Re-188 microspheres. This study suggests that a treatment dose of Re-188 microspheres causes transient inflammation of synovium without any detectable damage to the articular cartilage of knee joint.

Imaging of dopamine transporters (DATs) in the brain using [99Tcm]TRODAT-1 showed excellent pharmacokinetics for estimation of transporter concentrations. It has been reported that there may be differences in the binding kinetics of DAT radiotracers to DATs between normal subjects and patients with Parkinson's disease (PD). The aim of this study was to determine an optimal time point for (99Tcm]TRODAT-1 brain single photon emission tomography (SPET) acquisition that provides stable target to non-target ratios reflecting the DAT concentration in the brain. Serial [99Tcm]TRODAT-1 brain SPET images 2, 3 and 4 h after intravenous injection of [99Tcm]TRODAT-1 (925 MBq) were performed in five healthy subjects and nine PD patients. Regions of interests were drawn, and caudate/occipital (C/O) and putamen/occipital (P/O) specific to non-specific [99Tcm]TRODAT-1 binding ratios were calculated. The C/O and P/O ratios in healthy subjects showed consistent increases with time, but in PD patients, the C/O and P/O ratios of [99Tcm]TRODAT-1 reached a stable level at 3 h post-injection. There was a statistically significant difference (P < 0.001) between PD and normal subjects at 4 h post-injection for both the C/O and the P/O ratios. In conclusion, we recommend the acquisition of [99Tcm]TRODAT-1 SPET images at 4 h post-injection, as at this time point the C/O and P/O ratios can be used to discriminate between PD patients and healthy subjects.

Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h (n = 5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats (n = 5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.

The purpose of this study was to analyse the biodistribution of rhenium-188 Lipiodol in rats with hepatic tumours following intrahepatic arterial injection to assess the potential of188Re-Lipiodol as a radiopharmaceutical for the treatment of hepatic tumours in humans. Twelve male rats with hepatic tumours were killed at 1 h, 24 h and 48 h after injection of approximately 7.4 MBq of188Re-Lipiodol via the hepatic artery. Samples of various organs were obtained and counted to calculate the tissue concentration. Radioactivity in the hepatic tumours was very high throughout this study, with a biological half-life of 122.9 h. Radioactivity in the normal liver tissue was also high, but was significantly lower than in the tumour. The biological half-life in the normal liver tissue was 31.7 h. The ratio of tumour concentration to the normal liver tissue concentration was 5.15 at 1 h and rose to 7.7 at 24 h and 10.84 at 48 h. The level of radioactivity in the lung was high at 1 h, and declined rapidly over time. The level of radioactivity in the kidney was moderate throughout the study. The radiation concentrations in muscle, spleen, testis, bone and whole blood were insignificant. We conclude that188Re-Lipiodol should be considered as a potential radiopharmaceutical for the intra-arterial treatment of hepatic tumours.

PURPOSE: PEGylated liposomes are important drug carriers that can passively target tumor by enhanced permeability and retention (EPR) effect in neoplasm lesions. This study demonstrated that tumor burden determines the tumor uptake, and also the tumor response, in cancer treatment with PEGylated liposomal drugs in a C26/tk-luc colon carcinoma-bearing mouse model. METHODS: Empty PEGylated liposomes (NanoX) and those encapsulated with VNB (NanoVNB) were labeled with In-111 to obtain InNanoX and InVNBL in high labeling yield and radiochemical purity (all >90%). BALB/c mice bearing either small (58.4±8.0 mm(3)) or large (102.4±22.0 mm(3)) C26/tk-luc tumors in the right dorsal flank were intravenously administered with NanoVNB, InNanoX, InVNBL, or NanoX as a control, every 7 days for 3 times. The therapeutic efficacy was evaluated by body weight loss, tumor growth inhibition (using calipers and bioluminescence imaging) and survival fraction. The scintigraphic imaging of tumor mouse was performed during and after treatment. RESULTS: The biodistribution study of InVNBL revealed a clear inverse correlation (r (2) = 0.9336) between the tumor uptake and the tumor mass ranged from 27.6 to 623.9 mg. All three liposomal drugs showed better therapeutic efficacy in small-tumor mice than in large-tumor mice. Tumor-bearing mice treated with InVNBL (a combination drug) showed the highest tumor growth inhibition rate and survival fraction compared to those treated with NanoVNB (chemodrug only) and InNanoX (radionuclide only). Specific tumor targeting and significantly increased tumor uptake after periodical treatment with InVNBL were evidenced by scintigraphic imaging, especially in mice bearing small tumors. CONCLUSION: The significant differences in the outcomes of cancer treatment and molecular imaging between animals bearing small and large tumors revealed that tumor burden is a critical and discriminative factor in cancer therapy using PEGylated liposomal drugs.

In this study, we labelled Lipiodol with yttrium-90 and analysed the biodistribution in rats after intrahepatic arterial injection. An RP-18 column (E. Merck) was used to separate 90Y from strontium-90. 90Y was retained on the column, which had been pretreated with yttrium-selective extraction reagent, di(2-ethylhexyl) phosphate, while 90Sr was washed out. A hexadentate nitrogen-donor chelating ligand N,N,N',N'-tetrakis(2-benzymidazolylmethyl)-1,2-ethanediamine (EDTB) was synthesized by condensation of 1,2-benzenediamine and ethylene diamine tetra-acetic acid (EDTA). Lipiodol was covalently conjugated with EDTB. The final product was obtained by eluting the retained 90Y from the RP-18 column with EDTB-Lipiodol. Sixteen male rats (Sprague-Dawley) were sacrificed at 1 h, 24 h, 48 h and 72 h (four rats at each time) after injection of approximately 0.1 mCi 90Y-Lipiodol via the hepatic artery. Samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained and counted to calculate the tissue concentrations. In addition, labelling efficiency and in vitro stability were determined by ITLC methods. We found that at 1 h after intrahepatic injection, most of the radiotracer was retained in the liver, but it was eliminated gradually over a few days. The radioactivity level in the lung was fair at 1 h and remained at roughly the same level throughout the study. Radioactivity in the kidney and spleen reached a relatively high level at 24 h, but declined rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p0.05) was significantly better than those of 5-FU (48.25 days; p0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

Nanoliposomes are good drug delivery systems that allow the encapsulation of drugs into vesicles for their delivery. The objective of this study is to investigate the therapeutic efficacy of a new radio-therapeutics of (188)Re-labeled pegylated liposome in a C26 murine colon carcinoma solid tumor model. The safety of (188)Re-liposome was evaluated before radiotherapy treatment. The anti-tumor effect of (188)Re-liposome was assessed by tumor growth inhibition, survival ratio and ultrasound imaging. Apoptotic marker in tumor was also evaluated by the TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling) method after injection of (188)Re-liposome. The group treated with (188)Re-liposome displayed slight loss in body weight and decrease in white blood cell (WBC) count 7 to 14 days post-injection. With respect to therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI = 0.140; 80 day) than those treated with anti-cancer drug 5-FU (MGI = 0.195; 69 day) and untreated control mice (MGI = 0.413; 48 day). The ultrasound imaging showed a decrease in both tumor volume and number of blood vessels. There were significantly more apoptotic nuclei (TUNEL-positive) in (188)Re-liposome-treated mice at 8 h after treatment than in control mice. These results evidenced the potential benefits achieved by oncological application of the radio-therapeutics (188)Re-liposome for adjuvant cancer treatment.

The OLINDA/EXM computer code was created as a replacement for the widely used MIRDOSE3 code for radiation dosimetry in nuclear medicine. A dosimetric analysis with these codes was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) in colon carcinoma-bearing mice.Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine ((188)Re-BMEDA) and (188)Re-liposome were obtained for estimation of absorbed doses in normal organs. Radiation dose estimates for normal tissues were calculated using the MIRDOSE3 and OLINDA/EXM programs for a colon carcinoma solid tumor mouse model.Mean absorbed doses derived from(188)Re-BMEDA and (188)Re-liposome in normal tissues were generally similar as calculated by MIRDOSE3 and OLINDA/EXM programs. One notable exception to this was red marrow, wherein MIRDOSE3 resulted in higher absorbed doses than OLINDA/EXM (1.53- and 1.60-fold for (188)Re-BMEDA and (188)Re-liposome, respectively).MIRDOSE3 and OLINDA have very similar residence times and organ doses. Bone marrow doses were estimated by designating cortical bone rather than bone marrow as a source organ. The bone marrow doses calculated by MIRDOSE3 are higher than those by OLINDA. If the bone marrow is designated as a source organ, the doses estimated by MIRDOSE3 and OLINDA programs will be very similar.

The biodistribution, pharmacokinetics, dosimetry and comparative therapeutic efficacy of intravenously administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposome ((188)Re-liposome) and 5-FU were investigated in a CT26-luc lung-metastatic model. After intravenous administration of (188)Re-liposome, tumor accumulation from the radioactivity was observed. Levels of radioactivity in tumors were maintained at steady levels (from 5.40 to 5.67 %ID/g) after 4 to 24 h. In pharmacokinetics, the AUC((0→∞)), MRT((0→∞)) and Cl of (188)Re-liposome in blood via intravenous route were 998 h %ID/ml, 28.7 h and 0.1 ml/h, respectively. The total excreted fractions of feces and urine were 0.61 and 0.26, respectively. Absorbed doses for (188)Re-liposome in the liver and red marrow were 0.31 and 0.08 mSv/MBq, respectively. Tumor-absorbed doses for (188)Re-liposome ranged from 48.4 to 1.73 mGy/MBq at 10 to 300 g tumor spheres. In therapeutic efficacy, the survival times of mice after (188)Re-liposome [80% maximum tolerated dose (MTD); 29.6 MBq], 5-FU (80% MTD; 144 mg/kg), liposome or normal saline treatments were evaluated. Consequently, radiotherapeutics of (188)Re-liposome attained a longer lifespan (increase of 34.9%; P=.005) in mice than in the normal saline group. The increase in lifespan of the (188)Re-liposome group was 2.5-fold greater than that of the 5-FU group. Therefore, intravenous administration of (188)Re-liposome could provide a benefit and it is a promising strategy for delivery of passive nanotargeted radiotherapeutics in oncology applications.

Fifty patients (43 male, 7 female, age 31-77 years) with single solid masses in their lungs based on the findings of a chest X-radiograph [40 malignancies: 5 small cell carcinoma (Ca), 17 epidermoid Ca, 12 adeno Ca, 6 undifferentiated large cell Ca] and 10 benign lesions underwent technetium-99m (V) dimercaptosuccinic acid [99m-(V)DMSA] scans to evaluate the usefulness of 99mTc-(V)DMSA in the detection of lung Ca with different cell types and benign lesions. Only 43% (17/40) of the malignancies in the lungs were detected by 99mTc-(V)DMSA, including 29% (5/17) epidermoid Ca, 50% (6/12) adeno Ca and 17% (1/6) undifferentiated large cell Ca of the lungs. However, all 5 cases of small cell Ca and 11 cases combined with bone metastasis were revealed by 99mTc-(V)DMSA. In addition, 3 of the 10 benign lesions (2 organizing pneumonias, 1 benign tumor) presented with an uptake of 99mTc-(V)DMSA. The diagnostic sensitivity, specificity and accuracy were 43%, 70% and 48%, respectively, in differentiating malignant from benign lesions for the single solid mass in the lungs. In conclusion, 99mTc-(V)DMSA is of little or no use in the differentiation of lung Ca from single solid masses in the lungs.

A dosimetric analysis was performed to evaluate nanoliposomes as carriers of radionuclides ((188)Re-liposomes) and radiochemotherapeutic drugs [(188)Re-doxorubicin (DXR)-liposomes] in internal radiotherapy for colon carcinoma, as evaluated in mice.Pharmacokinetic data for (188)Re-N, N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), (188)Re-liposome, and (188)Re-DXR-liposome were obtained for the estimation of absorbed doses in tumors and normal organs. Two colon carcinoma mouse models were employed: subcutaneous growing solid tumor and malignant ascites pervading tumor models. Radiation-dose estimates for normal tissues and tumors were calculated by using the OLINDA/EXM program. An evaluation of a recommended maximum administered activity (MAA) for the nanotargeted drugs was also made.Mean absorbed doses derived from (188)Re-liposome and (188)Re-DXR-liposome in normal tissues were generally similar to those from (188)Re-BMEDA in intraperitoneal and intravenous administration. Tissue-absorbed dose in the liver was 0.24-0.40 and 0.17-0.26 (mGy/MBq) and in red marrow was 0.033-0.050 and 0.038-0.046 (mGy/MBq), respectively, for (188)Re-liposome and (188)Re-DXR-liposome. Tumor-absorbed doses for the nanotargeted (188)Re-liposome and (188)Re-DXR-liposome were higher than those of (188)Re-BMEDA for both routes of administration (4-26-fold). Dose to red marrow defined the recommended MAA.Our results suggest that radionuclide and chemoradiotherapeutic passive targeting delivery, using nanoliposomes as the carrier, is feasible and promising in systemic-targeted radionuclide therapy.

The pharmacokinetics and internal radionuclide therapy of intraperitoneally administrated (188)Re-N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin ((188)Re-DXR-liposome) were investigated in the C26 murine colon carcinoma ascites mouse model. After intraperitoneal administration of the nanotargeted bimodality (188)Re-DXR-liposome, the ascites and tumor accumulation of the radioactivity were observed, the levels of radioactivity within the ascites were maintained at relatively higher levels before 48 h and the levels of radioactivity in the tumor were maintained at steady levels after 4 h. The AUC((o-->infinity)) of (188)Re-DXR-liposome in blood, ascites and tumor was 9.3-, 4.2- and 4.7-fold larger than that of (188)Re-BMEDA, respectively. The maximum tolerated dose of intraperitoneally administrated (188)Re-DXR-liposome was determined in normal BALB/c mice. The survival, tumor and ascites inhibition of mice after (188)Re-DXR-liposome (22.2 MBq of (188)Re, 5 mg/kg of DXR) treatment were evaluated. Consequently, radiochemotherapeutics of (188)Re-DXR-liposome attained better survival time, tumor and ascites inhibition (decreased by 49% and 91% at 4 days after treatment; P

Nanoliposomes are useful carriers in drug delivery. Radiolabeled nanoliposomes have potential applications in radiotherapy and diagnostic imaging. In this study, the biodistribution and pharmacokinetics of 188Re-BMEDA-labelled pegylated liposomes (RBLPL) and unencapsulated 188Re-BMEDA administered by the i.v. route in murine C26-colon tumour-bearing mice were investigated. MicroSPECT/CT images were performed to evaluate the distribution and tumor targeting of RBLPL in mice. For the biodistribution study, the highest uptake of liposome in tumors was 3.62% +/- 0.73% at 24 h after RBLPL administration, and the tumor to muscle ratio of RBLPL was 7.1-fold higher than that of 188Re-BMEDA. With image analysis, the highest SUV in tumor was 2.81 +/- 0.26 at 24 h after injection of RBLPL. The Pearson correlation analysis showed a positive correlation of tumor targeting or uptake of RBLPL between biodistribution and microSPECT semi-quantification imaging analysis (r = 0.633). The results of the pharmacokinetics revealed that the area under the tissue concentration-time curve (AUC) of RBLPL was 4.7-fold higher than that of unencapsulated 188Re-BMEDA. These results suggested the potential benefit and advantage of 188Re-labeled nanoliposomes for imaging and treatment of malignant diseases.

Aim The aim of this study was to investigate the nigrostriatal dopaminergic function in patients with corticobasal degeneration (CBD) using [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2-1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]etanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]-[ 9 9 m Tc]technetium ([ 9 9 m Tc]TRODAT-1) brain single-photon emission tomography (SPET). Methods Five patients with probable CBD, 10 age- and duration-matched patients with idiopathic Parkinson's disease (IPD) and 10 age-matched healthy volunteers completed the SPET study. the images were obtained 4 h after intravenous Injection of 925 MBq of [ 9 9 m Tc]TRODAT-1. Using a magnetic resonance imaging atlas of the striatum, the ratios of specific striatal binding to non-specific occipital binding were calculated. Results Clinical analysis showed that the CBD patients obtained significantly higher scores on the Unified Parkinson's Disease Rating Scale and a significantly worse score for activities of daily living. In the CBD and IPD groups, striatum - occipital/occipital, caudate nucleus-occipital/occipital and putamen - occipital/occipital ratios decreased significantly relative to those of healthy subjects. No statistical difference could be found between the CBD and IPD groups for these ratios, although relatively even, decreased uptakes in the caudate nucleus and putamen were found in the CBD group. On further analysis of the index of binding reduction, the differences between the caudate nucleus and putamen were significantly lower in the CBD group than in the IPD group. The striatal uptake of [ 9 9 m Tc]TRODAT-1 showed a distinct asymmetry in both the CBD and IPD patients. Conclusion From this study, it can be concluded that early-stage CBD patients have a worse performance and more difficulties with daily activities than IPD patients. CBD patients demonstrated essentially similar patterns of [ 9 9 m Tc]TRODAT-1 binding as those with IPD. However, there was relatively more homogeneous involvement of the caudate nucleus and putamen in the CBD patients. This provides information about the differences between these patients in the early stages.

The imaging of dopamine transporter (DAT) with (99m)Tc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]-(99m)Tc-technetium) and SPECT has been recently proposed to be a valuable and feasible means of assessment of the integrity of dopamine neurons. The purpose of this study was to further investigate the clinical correlations and the age-specific sensitivity and specificity of this new approach in the diagnosis of patients with idiopathic Parkinson's disease (PD) that manifests in patients50 y of age.SPECT imaging with (99m)Tc-TRODAT-1 was conducted in 78 consecutive PD patients and in 40 age-matched healthy subjects. The images were obtained 4 h after the intravenous injection of the tracer. The ratios of specific striatal binding to nonspecific occipital binding were calculated. S/O represents the ratio for whole striatal binding, whereas P/O and C/O represent the putamen and caudate nucleus, respectively. Statistical analyses of the sensitivity and specificity of these ratios in different age-specific subgroups were performed. The correlations between these ratios and clinical assessments were also analyzed. The age-related declines in the striatal binding in both patients and controls were given particular focus.The S/O, C/O, and P/O ratios decreased significantly both contralaterally and ipsilaterally to the dominant symptomatic side in the PD group (P0.0001). The mean reduction of binding was found in the order of putamen (contralateral side, -81%; ipsilateral side, -67%) and caudate nucleus (contralateral side, -46%; ipsilateral side, -40%). The sensitivity and specificity of both P/O and S/O ratios were 100% in discriminating PD patients from healthy subjects in the age-specific groups. The binding ratios correlated negatively with the Unified Parkinson's Rating Scale and Hoehn and Yahr (H-Y) staging. Of particular interest, the binding of the striatum contralateral to the asymptomatic side in H-Y stage I patients also decreased significantly. The age-related decline of these ratios was significant in the control group.We have demonstrated that (99m)Tc-TRODAT-1 SPECT has a high sensitivity and specificity for measuring the decrement of DAT in PD patients. In addition to its wide availability, we suggest that this new approach may serve as a diagnostic marker for PD.

Functional brain imaging targeting the presynaptic dopamine nerve terminal of the nigrostriatal system has been used for monitoring disease progression and evaluating therapeutic effectiveness in patients with Parkinson's disease (PD). (99m)Tc-TRODAT-1 binds with high selectivity to the dopamine transporters in the striatum and can be imaged with SPECT 4 h after injection. We studied the test and retest reproducibility of (99m)Tc-TRODAT-1 SPECT measures in patients with PD to assess the reliability of (99m)Tc-TRODAT-1 for longitudinal evaluation of the nigrostriatal dopaminergic function.Each of 20 patients with PD underwent 2 (99m)Tc-TRODAT-1 SPECT scans at an interval of 2-3 wk. Patients were imaged 4 h after injection of 925 MBq (99m)Tc-TRODAT-1. Two imaging outcome measures were evaluated: the ratio of specific-striatal-to-nonspecific uptake and the striatal asymmetry index. For both measures, the test/retest variability was calculated. Reproducibility of the 2 outcome measures was evaluated in terms of intraclass correlation coefficient (ICC) and 95% limits of agreement.The mean ratio of specific-striatal-to-nonspecific uptake showed excellent test/retest reproducibility with a mean variability of 10.20%, an ICC of 0.95 (95% confidence interval = 0.88-0.98), and 95% limits of agreement, ranging from -0.19 to 0.19. The striatal asymmetry index had larger test/retest variability (60.41%), a slightly smaller ICC of 0.86 (95% confidence interval = 0.65-0.95), and a wider range of 95% limits of agreement (-16.09 to 15.19). In addition, there was a significant negative correlation between the mean ratio of specific-striatal-to-nonspecific uptake and the motor subscore of the Unified Parkinson's Disease Rating Scale in both test and retest conditions.Our data indicate that the imaging outcome expressed by the mean ratio of specific-striatal-to-nonspecific uptake has an excellent test/retest reproducibility and correlates with disease severity. These findings suggest that (99m)Tc-TRODAT-1 SPECT imaging is useful and feasible for measuring disease progression in PD.

Using (99m)Tc-TRODAT-1 ((99m)Tc-[2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]-oct-2-yl]-methyl](2-mercaptoethyl) amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT imaging, we measured striatal dopamine transporters (DATs) activity in multiple system atrophy (MSA) to investigate the possibility of differentiating it from Parkinson's disease (PD) and to correlate the findings with the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes of MSA.Forty-nine patients with probable MSA (30 MSA-P, 19 MSA-C), a disease control group of 36 age- and disease duration-matched patients with probable PD, and a healthy control group of 33 age-matched healthy volunteers participated in a SPECT study. The ratios of specific striatal binding-to-nonspecific occipital binding, including the striatum-to-occipital ratio (S/O), putamen-to-occipital ratio (P/O), caudate nucleus-to-occipital ratio (C/O), and putamen-to-caudate nucleus ratio (P/C), were calculated. The statistical analyses of uptakes among 4 groups used ANOVA followed by Games-Howell's multiple comparisons. The Spearman correlation coefficient between the motor scores of Unified Parkinson's Disease Rating Scale (UPDRS-III) and those binding ratios of the MSA-P and MSA-C groups and the PD group was also performed.The striatal binding was more symmetrically reduced in the MSA-P (asymmetric index, 14.2) and MSA-C (asymmetric index, 8.1) groups, in contrast to the greater asymmetric reduction in the PD group (asymmetric index, 28.6). Overall striatal binding was significantly reduced in the MSA-P (-59.8%), MSA-C (-29.9%), and PD (-58.0%) groups with no overlap between these values and those of the control group. Like the PD group, bilateral P/O, C/O, and S/O ratio values were significantly reduced in the MSA-P and MSA-C groups. Nevertheless, the reduction of bilateral P/O and S/O ratios was more for the MSA-P group than for the MSA-C group. P/C ratios showed that the MSA-P and PD groups had similar patterns of nigral impairment, but the MSA-C group had a different pattern. No correlation between the UPDRS-III scores and (99m)Tc-TRODAT-1 bindings was found in both MSA-P and MSA-C groups; in contrast, a significant negative correlation was noted in the PD group.(99m)Tc-TRODAT-1 brain SPECT is capable of scientifically differentiating between the MSA-P and MSA-C subtypes, and MSA-P has more symmetric nigrostriatal damage than that in PD. (99m)Tc-TRODAT-1 brain SPECT imaging probably could provide important information to differentiate MSA from PD.

To assess the feasibility and short-term outcome of intracoronary irradiation after pure balloon angioplasty (POBA) of de novo and post-POBA restenotic lesions with a liquid beta-emitter (188)Re-filled balloon.Nonrandomized prospective study with contemporaneous control group in a single medical center.In the Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis study, 40 patients underwent 14-Gy irradiation and 15 patients underwent 20-Gy irradiation at a tissue depth of 0.5 mm after POBA. Thirty control patients received a 5-min inflation with a perfusion balloon catheter after POBA.No procedural or in-hospital complications, or 30-day major adverse cardiac events were noted. Six-month angiographic restenosis rates were 49% in the 14-Gy group, 20% in the 20-Gy group, and 57% in the control group (p = 0.05, 20-Gy group vs control group). In the lesions with an arc of calcification of180 degrees, restenosis occurred in 15 of the 34 lesions (44%) in the 14-Gy group and in none of the 11 lesions (0%) in the 20-Gy group (p = 0.007). In a vessel with a reference diameter3.0 mm, restenosis occurred in 1 of the 8 lesions (13%) in the 20-Gy group, and in 8 of the 11 lesions (73%) in the control group (p = 0.02). In the post-POBA restenotic lesions, restenosis occurred in none of the six lesions (0%) in the 20-Gy group, and in five of the six lesions (83%) in the control group (p = 0.008).Post-POBA, catheter-based brachytherapy in nonstented native coronary artery with a (188)Re-filled balloon can effectively reduce target lesion restenosis with 20-Gy irradiation at a tissue depth of 0.5 mm and seems to be more effective in the treatment of lesions with an arc of calcification180 degrees, in a vessel with a reference diameter of3.0 mm, and in post-POBA restenotic lesions.

Patients who receive percutaneous transluminal coronary angioplasty (PTCA) are often haunted by restenosis of the target vessel within 6 months. Intracoronary irradiation has been shown to alter the luminal narrowing response after balloon angioplasty.The Taiwan Radiation in Prevention of Post-Pure Balloon Angioplasty Restenosis-I (TRIPPER-I) study evaluated the feasibility, safety, and 6-month angiographic restenosis with intracoronary irradiation after pure balloon angioplasty (POBA) of de novo and post-POBA restenotic lesions in native coronary arteries using a self-centering beta-emitter rhenium-188 (Re-188)-filled balloon.Forty patients received 14 Gy at a 0.5-mm tissue depth with a Re-188 solution-filled perfusion balloon catheter, and 25 control patients received 5-min inflation with a perfusion balloon catheter. There were no procedural complications or in-hospital or 30-day major adverse cardiac events. Six-month angiographic follow-up was performed on 39 Re-188 (97.5%) and 25 control patients (100%). The restenosis rate was 49% in the Re-188 and 56% in the control groups (p=0.62). The composite end-points of death, myocardial infarction, and target-vessel revascularization were 40% in the Re-188 group and 36% in the control group (p=0.80).Catheter-based radiotherapy after POBA of de novo and post-POBA restenotic lesions with a Re-188-filled balloon is feasible but was ineffective in reducing target lesion restenosis with a dose of 14 Gy delivered at a 0.5-mm tissue depth in this study.

Dopamine transporter (DAT) binding is decreased in Machado-Joseph disease (MJD) patients. To further investigate the DAT activity in asymptomatic MJD (aMJD) gene carriers, we performed this prospective study using (99m)Tc-TRODAT-1 ([(99m)Tc][2[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]-methyl](2-mercaptoethyl)amino]ethyl]amino]ethane-thiolato(3-)-N2,N2',S2,S2]oxo-[1R-(exo-exo)])) brain SPECT on 5 aMJD gene carriers, 10 age-matched MJD patients, and 10 age-matched healthy control subjects.Brain SPECT images were acquired 4 h after intravenous injection of 925 MBq (25 mCi) (99m)Tc-T RODAT-1, which is known to bind specifically to the DAT on the nigrostriatal terminals. By fusing these SPECT images with a striatal atlas, obtained from MRI, binding of this tracer in the entire striatum was measured and the uptake values in bilateral striatal areas were compared between these 3 groups.The uptake values of the aMJD gene carriers (P0.001) and MJD patients (P0.001) displayed a significant reduction compared with those of the control subjects. The reduction was more severe in the MJD patient group (P0.05). Bilateral putamen-to-caudate ratios were significantly lower in the aMJD gene carrier and MJD patient groups (P0.001). The dopamine neuronal activity, as represented by the tracer binding, was more prominently affected in the putamen in these patients and gene carriers.(99m)Tc-TRODAT-1 brain SPECT is capable of detecting early alteration of dopamine neurons in the striatal region. Significantly, the results suggest that this impairment of presynaptic dopamine function actually occurs at an early stage, which was previously unrecognized in these aMJD gene carriers.

The purpose of this study was to evaluate the contribution of the postsynaptic mechanism to the development of motor fluctuation in advanced Parkinson’s disease (PD). We used 123I-iodobenzamide single-photon emission computed tomography to measure the striatal dopamine D2 receptor densities in early levodopa-naïve PD, chronic PD with stable levodopa response, and advanced PD with fluctuating levodopa response. The basal ganglia/frontal cortex ratios at both hemispheres were calculated and averaged. PD patients with fluctuating levodopa response showed a significant decrease in striatal dopamine D2 receptor densities compared to those with early (1.57 ± 0.20 vs. 1.77 ± 0.12, p = 0.009) or chronic stable PD (1.57 ± 0.20 vs. 1.77 ± 0.10, p = 0.024). We conclude that the decreased D2 receptor densities in advanced PD reduced the ‘safety factor’ for synaptic transmission and contributed to the development of motor fluctuation.

Background. Intravascular brachytherapy is an effective method for inhibiting coronary restenosis after percutaneous transluminal coronary angioplasty. A new concept for preventing restenosis is the use of a liquid-filled balloon containing a beta-ray-emitting radioisotope. Generator-produced rhenium-188 (Re-188) is a good candidate for intravascular brachytherapy. However, in the unlikely event of balloon rupture, release of Re-188 perrhenate may cause a high radiation dose to the thyroid and stomach. In this study, we compared the biodistributions of three Re-188 preparations (Re-188 perrhenate, Re-188 pentetic acid [DTPA], and Re-188 MAG3) to assess the radiation dose to organs in a rat model that mimicked balloon rupture. Methods and Results. After injection of Re-188 preparations intravenously, rats were killed at 10 minutes, 30 minutes, 60 minutes, 2 hours, and 6 hours (n = 5/group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter. In addition, urine excretion and thyroid gland uptake were evaluated in rats (n = 5/group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed all 3 agents were excreted primarily via urine. In the Re-188 MAG3 group, 82% was excreted within 1 hour, but in the Re-188 perrhenate group, only 28% was excreted. The biodistribution data for these agents revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA and Re-188 MAG3 groups. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for all 3 agents. The thyroid radiation values were 0.163, 0.0167, and 0.00728 mGy/MBq for Re-188 perrhenate, Re-188 DTPA, and Re-188 MAG3, respectively. The stomach radiation values were 0.127 mGy/MBq for Re-188 perrhenate, 0.013 mGy/MBq for Re-188 DTPA, and 0.0104 mGy/MBq for Re-188 MAG3. Conclusions. In the event of balloon rupture, the release of Re-188 MAG3 or Re-188 DTPA results in lower radiation doses than release of Re-188 perrhenate, especially to the thyroid gland and the stomach. (J Nucl Cardiol 2000;7:37–42.)

Rhenium-186 (Re-186) hydroxyethylidene diphosphonate (HEDP) has been shown to localize in metastatic foci within bone in a manner similar to Tc-99m bone-seeking agents. Usually, in the preparation of diagnostic Tc-99m radiopharmaceuticals, the concentration of Tc is at trace level (10 −8 M). However, large amounts of carrier are included in the preparation of Re-186 radiopharmaceuticals (10 −4 M), which may significantly affect the preparation of Re-HEDP. In this study, Re-188 was used as an Re tracer. The effects of pH and concentrations of Re carrier on the preparation of Re-HEDP were investigated. Re-188-Sn-HEDP was prepared by reconstitution of a kit of lyophilized HEDP mixture, and tin chloride with a radioactive solution of perrhenate in saline. The total concentration of Re present in this work ranged from 10 −8 to 10 −3 M. The results showed that high labeling efficiency was obtained for each preparation. Although the chemical behaviors of the Re-188 HEDP complexes, with and without carrier, were similar, the biodistribution patterns of carrier free Re-188 HEDP in rats were found to differ from the biodistribution patterns of carrier-added Re-188 HEDP.

The search for an ideal radioisotope for systemic radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays and having a short physical half-life of 16.9 h, rhenium-188 is a very good potential candidate for systemic radiotherapy. In this study, we labeled hydroxyethylidene diphosphonate (HEDP) with 188Re and analyzed the biodistribution and bone uptake following intravenous injection in rats to assess its potential for clinical use. The rats were injected with approximately 14.8 MBq (0.4 mCi) 188Re-HEDP in a volume of 0.1 ml intravenously and then sacrificed at 1 h, 24 h, or 48 h (four rats at each time). Samples (about 0.1 g) of lung, liver, kidney, spleen, testis, muscle, stool, and bone (thoracic vertebra) were taken and weighed carefully. In addition, a 1-ml sample of blood was drawn from the heart and 1 ml of urine was taken from the urinary bladder immediately after killing. Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (% ID/g or ml). Bone lesions were created in the right tibial bone in three rabbits to calculate the lesion to normal uptake ratio (L/N ratio). The biodistribution data showed that the radioactivity in the bone tissue was as high as 1.877% ID/g at 1 h and that it climbed to 2.017% ID/g at 4 h. The activity level in the kidney was highest at 1 h but declined rapidly throughout the study. The radioactivities in the lung, liver, muscle, spleen, testis, blood, and stool were all lower than 0.3% ID/g at 1 h and also declined rapidly. The biological half-life in bone was the longest (60.86 h). In contrast, the biological half-lives in muscle and blood were short (2.99 h and 6.21 h respectively). The concentrations of radioactivity in muscle, spleen, testis, and stool were quite low throughout the study. Most of the radiotracer was excreted by the urinary system. The L/N ratio was 4.23+/-0.21 in rabbits injected with 188Re-HEDP and 4.25+/-0.23 in those injected with technetium-99m methylene diphosphonate. In conclusion, we would suggest that 188Re-HEDP is a very good potential candidate for the treatment of bone metastases because of the following characteristics: (1) it is generator produced; (2) it has a short half-life; (3) it emits gamma rays suitable for imaging; (4) there is highly selective uptake in the skeletal system and bone lesions; and (5) it has a low non-target uptake and rapid clearance in nonosseous tissue.

In this study we prepared and analyzed the biodistribution of 188 Re-labelled Lipiodol ([ 188 -Re]-Lipiodol) in rats after intrahepatic arterial injection. EDTB was synthesized by condensation of 1,2-benzenediamine and ethylenediaminetetraacetic acid (EDTA). The labelling efficiency of [ 188 Re] Lipiodol was determined to be greater than 97% by ITLC developed with n -hexane. Following incubation of the [ 188 Re] Lipiodol with an equal volume of serum at 37°C for 48 h, ITLC indicated good in vitro stability. Approximately 7.4 MBq [ 188 Re] Lipiodol was injected in each rat via the hepatic artery and samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained. [ 188 Re] Lipiodol tissue concentrations showed that after 1 h intrahepatic injection most of the radiotracer was retained in the liver, and was eliminated slowly with a biological half-life of 33.5 h. Radioactivity levels in the lung, kidney and blood were moderate at 1 h, and declined rapidly over time. In the spleen, muscle, testis and bone, radiation levels were insignificant. These initial results indicate that [ 188 Re] lipiodol may be a potential radiopharmaceutical agent for the treatment of liver tumors.

Radiation synovectomy has been shown to be an effective treatment for the rheumatoid arthritic knee. In this study, we evaluated the suitability of rhenium-188 as a radiation synovectomy agent. In addition, we were successful in labelling sulphur colloid with 188Re. In vitro stability tests revealed that more than 95% of the 188Re remained in colloid form over a 3-day period. Intra-articular injection of 188Re sulphur colloid into arthritic rabbit joints was followed by gamma camera imaging to quantify the leakage. The mean retention percentages of 188Re colloid in arthritic knees were 93.7% (+/- 1.4%), 90.8% (+/- 1.7%) and 87.2% (+/- 0.6%) at 1 h, 1 day and 2 days, respectively. A biodistribution study of the arthritic rabbits revealed that the highest activity outside the knees was in the liver and the kidneys. Our preliminary results indicate that 188Re sulphur colloid may be an effective radiopharmaceutical for radiation synovectomy.