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PubMed1995

Preparation, biodistribution and dosimetry of copper-64-labeled anti-colorectal carcinoma monoclonal antibody fragments 1A3-F(ab')2.

UNLABELLED: Antibody fragments labeled with a radiometal using bifunctional chelates generally undergo renal clearance followed by trapping of the metabolites, leading to high radiation doses to the kidneys. Copper-64-labeled BAT-2IT-1A3-F(ab')2 was recently reported to accumulate in colorectal tumors in an animal model, however, kidney uptake was also high. In this study, the preparation of 64Cu-BAT-2IT-1A3-F(ab')2 was optimized to reduce the renal uptake. METHODS: The bifunctional chelate 6-bromoacetamidobenzyl-1,4,8,11-tetraazacyclotetradecane-N,N ',N",N'"-tetraacetic acid (BAT) was conjugated to 1A3-F(ab')2 using the linking agent 2-iminothiolane (2IT). The conjugation reaction produced 20% of a lower molecular weight (molecular wieght) impurity found to be TETA-1A3-Fab'. The conjugation procedure was optimized to include FPLC purification of the BAT-2IT-1A3-F(ab')2 from TETA-1A3-Fab' after conjugation prior to labeling with 64Cu. The biodistribution of 64Cu-labeled FPLC-purified and unpurified conjugates was determined in normal Sprague-Dawley rats and tumor bearing Golden Syrian hamsters. Human absorbed doses were calculated from rat biodistribution data and PET imaging of a baboon. RESULTS: Upon FPLC purification of the BAT-2IT-1A3-F(ab')2, the immunoreactivity of 64Cu-labeled 1A3-F(ab')2 was significantly improved over that of non-FPLC-purified 64Cu-BAT-2IT-1A3-F(ab')2, and the kidney uptake was decreased in normal rats. The biodistribution in hamsters showed some improvement in both tumor uptake and kidney clearance with FPLC-purified 64Cu-BAT-2IT-1A3-F(ab')2. CONCLUSION: The improved dosimetry of 64Cu-labeled FPLC purified BAT-2IT-1A3-F(ab')2 should more readily allow this agent to be investigated clinically to image colorectal cancer using PET.

Animals↗
PubMed1994

High-resolution PET imaging and quantitation of pharmaceutical biodistributions in a small animal using avalanche photodiode detectors.

UNLABELLED: The feasibility of high-resolution PET using BGO-avalanche photodiode detectors for in vivo imaging and quantitation of the biodistribution of radiopharmaceuticals in small animals is demonstrated. A prototype PET camera consisting of two scanning arrays of eight EG&G C30994 solid-state scintillation detectors was used to simulate a 310-mm diameter dual-ring animal tomograph having a 130-mm port and three imaging slices, each about 3.5 mm thick. The spatial resolution (FWHM) is 3 mm or less, isotropic and uniform throughout the 120-mm diameter field of view. METHODS: Female Fischer 344/CRBL rats implanted with subcutaneous mammary adenocarcinoma tumors were injected with copper-tetrasulfophthalocyanine (CuPcS4), a potential sensitizer for the photodynamic therapy of cancer, labeled with 64Cu (T1/2 = 12.7 hr, beta +:19%). RESULTS: In spite of the low specific radioactivity of 64Cu and other inherent limitations, organs such as the liver, kidneys and the tumor could be resolved with sufficient detail for their separation and quantitation. Apart from the tumor, agreement was obtained between the biodistributions measured by PET and by scintillation counting. The discrepancy for the tumor measurement results from averaging the radioactivity over the entire tumor volume when, in fact, CuPcS4 does not completely penetrate the tumor. This incomplete penetration is noted on the PET images. CONCLUSIONS: PET based on avalanche photodiode detectors provides an accurate measurement of target organ and tumor tissue concentrations. These preliminary results demonstrate the potential of very high resolution PET for biodistribution studies in small animals.

Animals↗
PubMed1993

SIMS microscopy imaging of the intratumor biodistribution of metaiodobenzylguanidine in the human SK-N-SH neuroblastoma cell line xenografted into nude mice.

Microdosimetric evaluations of targeted radiotherapy of neuroblastoma with metaiodobenzylguanidine (MIBG) require precise assessment of the intracellular and intratumor distribution of the drug. We report the use of secondary ion mass spectrometry (SIMS) microscopy, a technique capable of mapping any chemical element within a biological specimen, to determine 127I-MIBG biodistribution in human neuroblastoma SK-N-SH xenografted into nude mice. Highly specific images of 127I-MIBG biodistribution were mapped within the tumor after in vivo administration of the drug and sample processing with cryotechniques (high-speed freezing and cryo-embedding), which prevent MIBG diffusion from original sites of uptake. We showed that the biodistribution of the tracer was highly nonuniform within the tumor. At the cellular level, most of the drug accumulated in the cytosol and perinuclear areas. In contrast, chemical sample processing provided not only a considerable loss in sensitivity due to passive diffusion of the drug in the organic solvents, but also artefactual images mainly due to MIBG redistribution onto the cell nuclei. Based on our findings in this SK-N-SH experimental tumor model, we suggest that MIBG should be attached to long-range emitters, in the hope of irradiating the many tumorous areas that remain carrier-free.

3-Iodobenzylguanidine↗
PubMed1996

Monoclonal antibodies labeled with rhenium-186 using the MAG3 chelate: relationship between the number of chelated groups and biodistribution characteristics.

UNLABELLED: Our previous studies on the preparation of 186Re-MAb conjugates for clinical radioimmunotherapy (RIT) were extended with the aim to derive conjugates which have a high Re:MAb molar ratio, are stable in vitro and in vivo, have favorable biodistribution characteristics and can be used together with 99mTc-MAb conjugates as a matched pair in combined radioimmunoscintigraphy/RIT studies. METHODS: Rhenium and 99mTc-conjugates of intact MAb E48 were prepared according to our previously described multistep procedure using the MAG3 chelate and analyzed by protein mass spectrometry for the number of chelate molecules coupled to the MAb. For biodistribution analysis, tumor-free nude mice were simultaneously injected with 186Re-, 99mTc/99Tc- and/or 125I-labeled E48 IgG and dissected 1-48 hr postinjection. RESULTS: Rhenium-186-MAb conjugates with up to 20 Re-MAG3 groups per MAb molecule were prepared with an overall radiochemical yield of 40%-60%. The conjugates did not contain empty MAG3 groups and no aggregates were formed. Only conjugates with a 186Re-MAG3:MAb molar ratio higher than 12 demonstrated slightly impaired immunoreactivity to a maximum of 15% decrease at the 20:1 molar ratio. Biodistribution experiments revealed that a proportion of the conjugate became rapidly eliminated from the blood for conjugates with a Re-MAG3:MAb molar ratio higher than 8. In this case, an increased uptake of activity was observed in the liver and intestines. The 99mTc/99Tc-MAb conjugates showed a similar enhanced blood clearance when containing more than eight Tc-MAG3 groups, while dual labeling of MAbs revealed that the in vivo stability of the conjugated Re-MAG3 complex itself does not differ from the corresponding Tc-MAG3 complex. CONCLUSION: With the method described in this study, it is possible to prepare 186Re-MAG3-MAb conjugates that fulfil all the aforementioned criteria for use in clinical RIT. Coupling of too many metal-MAG3 groups to MAbs results in rapid blood clearance. At the same metal-MAG3:MAb molar ratio, 99mTc/99Tc-MAb conjugates show a similar pharmacokinetic behavior as 186Re-MAb conjugates and can thus be used to predict the localization of 186Re-labeled MAbs and make dosimetric predictions in individual patients.

Animals↗
PubMed1997

Biodistribution of the Cuban anti-meningococcal vaccine, VA-MENGOC-BC, in Balb/c mice.

VA-MENGOC-BC is the Cuban vaccine against Neisseria meningitidis BC. Its iodination and biodistribution measurement in Balb/c mice were the main goals of this study. The Chloramine-T method was effective for radiolabelling the proteoliposome, the main vaccine structure. The biodistribution demonstrated that the thyroid (50.4%), muscle (21.5%) and regional lymph nodes (20.5%) were the most radioactive organs and the kinetic of radioactivity was correlated with the primary (muscle, highest values in the first 3 days and lymph nodes, in the first 7 days) and secondary (muscle and lymph nodes, highest values in the first day) response. Early occurrence of slight radioactivity in the spleen was also observed. This was the first time that the iodination and biodistribution of this vaccine was carried out. The present study corroborated that the time selected in previous trials to obtain the lymph nodes and spleen cell, after a first (7 days) and second (3 days) dose, was actually the optimal for in vitro studies.

Animals↗
PubMed1997

Biodistribution and pharmacokinetics of 131I-labeled LEX 032, a recombinant hybrid of antichymotrypsin.

Pharmacokinetic and biodistribution studies were conducted in rats on a novel serine protease inhibitor, LEX 032, that was radiolabeled with 131I by the Bolton-Hunter reagent. LEX 032, a genetically engineered recombinant human nonglycosylated serpin, has been shown to have antiinflammatory properties in a number of animal models of inflammation and reperfusion injury. When 131I-LEX 032 was injected intravenously, a rapid whole body clearance of radioactivity was seen. Blood clearance followed a similar pattern. Forty-eight hours postinjection, 2.00 +/- 0.65 of the administered dose remained in the body. Greater than 59% of the radio-activity was excreted in the urine within the first 24 hr. Little radioactivity was found in the feces. With the exception of the thyroid, no significant organ-related uptake was noted. Radioactivity in the liver peaked at 20 min postinjection, with 1.00 +/- 0.13% administered dose/g and approximately 10% administered dose in the whole liver. At 1 hr, uptake in the kidney (9.30 +/- 1.52% administered dose/g) was the highest among all tissues, except for the thyroid. Gamma camera images were consistent with the biodistribution pattern. Pharmacokinetics and biodistribution were not affected by the dose of LEX 032 and were quite different from those of glycosylated wild type antichymotrypsin. These data indicate that LEX 032 exhibits the pharmacokinetics expected of a nonglycosylated 45 kDa protein.

Animals↗
PubMed1998

Effect of a chemotherapeutic drug on the biodistribution of 99mTc-DTPA in Balb/c mice.

The biodistribution of radiotracers used in diagnostic imaging can be grossly and recognizably altered by a wide variety of drugs and other treatment modalities, such as surgery and radiotherapy. Knowledge of such altered biodistribution is important both in making diagnostic inferences from scans and in dosimetric considerations. Vincristine is a drug that has been used as a component of many chemotherapeutic regimens because of its relative lack of hematologic toxicity. Its mechanism of action is by interfering with microtubule formation. The metabolic fate of vincristine has not been clearly determined and apparently undergoes in vivo decomposition. We have studied the effect of vincristine on the biodistribution of the 99mTc-DTPA. Vincristine was administered by ocular plexus via into female isogenic Balb/c mice. One hour after the last dose, 99mTc-DTPA (7.4 MBq) was injected and after 0.5 hour the animals were rapidly sacrificed. The organs were isolated, the radioactivity uptakes determined in a well counter and the percentages of radioactivity (% rad) in the organs calculated. The results have shown that the percentage rad has not been significantly altered in pancreas, thyroid and brain whilst a significant increased in thymus, ovary, uterus, spleen, kidney, heart, stomach, lung, liver and bone was reported. The results could be explained by the metabolization and/or therapeutic and immunosuppressive action of vincristine.

Animals↗
PubMed1997

Biodistribution of iodine-125 labeled monoclonal antibody/interleukin-2 immunoconjugate in athymic mice bearing human tumor xenografts.

BACKGROUND: Some vasoactive drugs have been studied in the hope of altering the vascular permeability and/or blood of tumors to enhance monoclonal antibody (MoAb) uptake. The pretreatment of interleukin-2 (IL-2), one of the vasoactive reagents, produced a generalized vascular permeability, but its function was not tumor specific. Conversely, MoAb/IL-2 immunoconjugates were developed that selectively alter the vasopermeability of tumors. In the current study the authors evaluated whether radiolabeled anti-carcinoembryonic antigen (CEA) MoAb, ZCE025/IL-2 immunoconjugate, specifically can enhance delivery of iodine-125 (I-125) to tumor sites. METHODS: ZCE025 was conjugated with IL-2, and the conjugate then labeled with I-125. Biodistribution studies were performed in athymic mice bearing CEA-producing human tumor (MKN45) xenografts. Mice were injected with I-125-ZCE025/IL-2 conjugate, and I-125 activities in the organs, including blood and tumor, were investigated at 1, 3, and 5 days after injection. Vascular permeability of the organs, including tumors, also was studied by using I-131 labeled mouse serum albumin in three groups. RESULTS: I-125 labeled ZCE025/IL-2 conjugate destroyed its lymphokine-activated killer cell (LAK) activation, but retained a minimum of 75% of the antibody binding reactivity. Biodistribution of I-125-ZCE025/IL-2 conjugate showed increased uptake of I-125 in tumor by a factor of 1.5, 4.2, and 4.1 compared with I-125-ZCE025 on Days 1, 3, and 5, respectively. In contrast, I-125 distribution was not enhanced in any organs except the tumor. Vascular permeability studies demonstrated that the physiologic effect of IL-2 was tumor specific in the mice that received the I-125-ZCE025/IL-2 conjugate. CONCLUSIONS: These studies indicate that the administration of radiolabeled MoAb/IL-2 double conjugate may enhance the therapeutic potential of radiolabeled MoAb without any pretreatment with IL-2 or repeated injection of MoAb.

Animals↗
PubMedDate not supplied

A model to evaluate the biological effect of natural products: vincristine action on the biodistribution of radiopharmaceuticals in BALB/c female mice.

Natural products have been widely used by human beings. However, sometimes the biological effects of these products are not fully known. We are trying to develop a model to evaluate the toxicity of compounds employed as therapeutic drugs. This model is based on the capability of natural products to alter the biodistribution of radiopharmaceuticals labelled with technetium-99m (99mTc). The acceptance of 99mTc-labelled radiopharmaceuticals is so rapid and its current use so diverse that it is not possible to study this radionuclide's behaviour in the body more deeply. There is evidence that the biodistribution or the pharmacokinetics of radiopharmaceuticals can be modified by some drugs, by pathological states, by irradiation and by surgical procedures. A lack of knowledge of such factors can induce a misvisualization of the scintigraphic images, leading to a misdiagnosis. Vincristine is a natural product that has been employed in various chemotherapeutic protocols in oncology. We have studied the effect of vincristine on the distribution of [99mTc]methylenediphosphonic acid ([99mTc]MDP) in female mice. After the last dose of vincristine, [99mTc]MDP was injected, the animals were sacrificed and the percentage of radioactivity (%ATI) was determined in the isolated organs. The %ATI was significantly decreased in the uterus, ovary, spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, liver, pancreas, stomach, heart, brain and bone of the animals treated with the natural product. Several biological effects have been reported in patients treated with vincristine. These effects could justify the alterations in the uptake of the radiopharmaceutical in specific organs. Moreover, these results have shown that it is possible to employ this model to evaluate the toxicity of drugs.

Animals↗
PubMed1992

Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin.

BACKGROUND: This study evaluated the effects of an association of ethiodized oil (Lipiodol Ultra Fluide, Laboratoires Guerbet, Aulnay-sous-Bois, France), with or without gelatin sponge, with doxorubicin (Adriamycin, Adria Laboratories, Columbus, OH) on the biodistribution and kinetics of doxorubicin during intraarterial injection. METHODS: Eighteen patients with hepatocellular carcinoma on cirrhotic liver received a therapeutic injection into the hepatic artery of 50 mg of doxorubicin alone (Group 1; n = 4), or emulsified in 10 ml of ethiodized oil and 2.5 ml of ioxaglate (Hexabrix, Laboratoires Guerbet) with (Group 2; n = 7) or without (Group 3; n = 7) gelatin sponge embolization. Before treatment, the absence of intrahepatic shunts was verified by an injection of technetium-labeled albumin macroaggregates. The biodistribution of doxorubicin was studied on two fronts: (1) pharmacokinetic--by measurement of the doxorubicin blood level during the 48 hours after injection; and (2) scintigraphic (2 mg of doxorubicin were labeled with 2 mCi of iodine 131)--by examination of the scintigrams and calculation of the following parameters: tumours liver/nontumorous liver binding ratio (T/NT ratio), liver/liver+lungs+abdomen binding ratio, and doxorubicin half-life in tumorous tissue. RESULTS: Pharmacokinetics results showed the following: the peak plasma concentration was significantly higher in Group 1 as compared with Groups 2 or 3 (Group 1: 2.1 +/- 0.9 mg/ml; Group 2: 0.9 +/- 0.3 mg/ml; Group 3: 0.5 +/- 0.2 mg/ml); the area under curve calculated from time zero to 1 hour was lower in Groups 2 and 3 compared with Group 1. Examination of the scintigrams showed the following: diffuse activity throughout the organism (Group 1), diffuse activity with strong hepatic and tumorous binding (Group 2), and mostly hepatic and tumoral binding (Group 3). The liver/liver+lungs+abdomen binding ratio was 28% +/- 1% in Group 1, 36% +/- 5% in Group 2, and 63% +/- 7% in Group 3. The T/NT ratios were 1.0 +/- 0 (Group 1), 1.5 +/- 0.1 (Group 2), and 4.7 +/- 0.5 (Group 3). The doxorubicin half-lives in tumourous tissue were 0.7 +/- 0.1 days (Group 1), 1.8 +/- 0.2 days (Group 2), and 2.6 days (n = 1; Group 3). CONCLUSIONS: This study shows (1) that the association of ethiodized oil with doxorubicin lowers the peak concentration of doxorubicin and increases the intratumoral concentration and half-life of doxorubicin, and (2) that these kinetic ameliorations are even more pronounced after embolization. Therefore, from a kinetic standpoint, the doxorubicin-ethiodized oil-gelatin sponge association is the best.

Aged↗
PubMed1994

Comparative biodistribution and radioimmunotherapy of monoclonal antibody RS7 and its F(ab')2 in nude mice bearing human tumor xenografts.

BACKGROUND: RS7 is a murine monoclonal antibody immunoglobulin G1 with pan-carcinoma reactivity, which was raised against human squamous cell carcinoma of the lung. To optimize the use of monoclonal antibody RS7 as a carrier of radionuclides for tumor targeting and therapeutic applications, whole RS7 immunoglobulin G and its F(ab')2 fragment were radiolabeled, and their biodistribution and effectiveness as radioimmunotherapeutic agents in nude mice bearing established human tumor xenografts were evaluated. The contributions of the tumor model, monoclonal antibody form (fragment vs. intact), radioisotope (131I, 111In, 90Y, and 188Re), and antigen target were evaluated. METHODS: Cumulative absorbed radiation doses were calculated from biodistribution data, and doses were normalized to blood to estimate expected relative toxicities. Two tumor models expressing different levels of RS7-antigen were studied: ME180, a cervical carcinoma cell line, and Calu-3, an adenocarcinoma of the lung cell line. In addition, the therapeutic effectiveness of 131I-RS7-F(ab')2 was compared to that of 131I-RS7-IgG. RESULTS AND CONCLUSIONS: Doses delivered to tumor (normalized to blood) calculated for 131I-RS7-F(ab')2 and 90Y-RS7-IgG were 4.7 times and 1.8 times greater, respectively, than 131I-RS7-IgG, and therefore would be expected to yield greater therapeutic efficacy when equitoxic doses are administered. This expectation was confirmed in the radioimmunotherapy study with 131I-RS7-F(ab')2. At equivalent absorbed dose to tumor, 131I-RS7-F(ab')2 was found to effect a slightly longer suppression of tumor growth than the intact 131I-RS7 IgG, and a 50% dose escalation yielded tumor regression for a prolonged period with the fragment, whereas a similar 50% dose escalation with 131I-RS7-IgG could not be tolerated.

Adenocarcinoma↗
PubMed1995

Characterization and biodistribution of a mouse/human chimeric antibody directed against pancreatic cancer mucin.

BACKGROUND: Nd2 is a murine monoclonal antibody (MoAb) directed against purified mucins of the human pancreatic cancer cell line SW1990. The authors previously reported promising results with Nd2 for immunotargeting pancreatic cancer. However, murine MoAbs induce human anti-mouse antibodies (HAMAs), a serious problem for clinical use. Mouse/human chimeric antibodies may be less immunogenic and therefore reduce the incidence of HAMAs. In this study, the binding affinity, tumor specificity, biodistribution, and immunoimaging of chimeric Nd2 were evaluated. METHODS: The affinity of chimeric Nd2 was evaluated by competition radioimmunoassay and Scatchard analysis using 125I-chimeric Nd2, 125I-murine Nd2, and SW1990 mucin. Immunoreactivity against pancreatic cancer tissues was examined histochemically by the avidin-biotin peroxidase complex method. The biodistribution of the MoAbs was examined in athymic nude mice bearing SW1990 xenografts that were administered intravenous 125I-labeled chimeric or murine Nd2. 111In-chimeric Nd2 was injected into the same xenograft models, and scintigrams were obtained on day 3. RESULTS: Affinity analysis and immunohistochemical studies showed that chimeric Nd2 had the same affinity to SW1990 mucin and the same specificity for pancreas cancer tissues as murine Nd2. Intravenous administration of 125I-chimeric Nd2 resulted in a maximum tumor accumulation of 43% of the initial dose/gram of tumor, which was almost identical to the accumulation of 125I-murine Nd2. Distinct immunoscintigrams of tumors in nude mice were obtained with 111In-chimeric Nd2. CONCLUSION: Chimeric Nd2 may have clinical potential in the radioimmunodetection and immunotherapy of pancreatic cancer.

Animals↗
PubMed1988

Biodistribution of a monoclonal antibody-methotrexate conjugate (791T/36-MTX) in patients with colorectal cancer.

The monoclonal antibody (MAb) 791T/36 which has previously been shown to localise in colorectal cancer has been conjugated to methotrexate (MTX) for potential use as a chemotherapeutic agent in malignant disease. To examine its biodistribution and tumour localisation, 16 patients with primary colorectal cancer were injected intravenously with 131I-labelled 791T/36-MTX conjugate and imaged using a gamma camera after 48-72 hr. Serial blood samples were taken to determine the levels of circulating conjugate and samples of tumour and normal colon were assayed for uptake of radioactivity. Whole body biodistribution, visualised by gamma scintigraphy, and blood clearance of both the antibody and drug moieties of 791T/36-MTX were similar to that previously found with unconjugated antibody. Assays of tissue radioactivity showed positive tumour uptake of drug-antibody conjugate (T:NT greater than 1.9:1) in 13/15 primary tumour specimens (median T:NT = 2.9:1). These studies indicate that 791T/36-MTX conjugates may have potential in the treatment of metastatic colorectal carcinoma.

Aged↗
PubMed2003

Biodistribution study of phosphonolipids: a class of non-viral vectors efficient in mice lung-directed gene transfer.

BACKGROUND: A multitude of cationic lipids have been synthesized since they were first proposed for use in gene therapy. Cationic lipids are able to efficiently transfect cells both in vitro and in vivo. Whereas most research groups have focused their investigations on the toxicity of these molecules, and on the location of expression of the DNA transferred by these vectors, little has been done to determine their biodistribution and elimination pathways. Our group has developed a family of cationic lipids termed phosphonolipids. Following a large in vitro screening experiment, we have selected several molecules for in vivo testing, with some of these phosphonolipids forming lipoplexes efficient in transfecting mouse lungs. It was thus of interest to study their fate after intravenous injection. METHODS: The respective biodistributions of both the GLB43 phosphonolipid and plasmid DNA were investigated and compared with DNA expression sites. Using the optimal conditions determined for phosphonolipids, we followed the gene transfer agent and plasmid DNA distributions versus time by radiolabeling them with (14)C and (32)P, respectively. Otherwise, we performed imaging by radiolabeling plasmid DNA with (99m)Tc. RESULTS: The lipoplexes appear to be directly located in the lung after administration. Secondly, the plasmid is released mainly into the lungs and the phosphonolipid vector is rapidly degraded. The hydrophilic moiety of the phosphonolipid is eliminated in the urine, as is the free plasmid. CONCLUSIONS: This study reveals that there are slight differences in the observed results depending on the technique used to label the DNA; secondly, results show that the residence time of phosphonolipids in the mouse body is related to the DNA binding time.

Animals↗
PubMed1994

Preparation and biodistribution of copper-67 complexes with tetradentate Schiff-base ligands.

Uncharged, lipophilic, low molecular weight copper complexes labeled with generator-produced copper-62 are of interest as potential radiopharmaceutials for imaging the brain with positron emission tomography (PET). We report here the synthesis and biodistribution of a series of [67Cu]copper(II) complexes with tetradentate N2O2(2-)Schiff-base ligands. The compounds studied varied in lipophilicity from log P = 1.7 to log P = 3.6, where P is the octanol/water partition coefficient. In rat biodistribution studies the tracers were generally found to penetrate the blood-brain barrier following intravenous injection, but some far better than others. For closely related compounds brain uptake at 1 min postinjection increased with increasing lipophilicity, although log P was clearly not the sole determinant of high brain uptake. Substantial variations were also observed in the rate at which these various compounds are cleared from brain, with a few exhibiting the prolonged cerebral retention of tracer that would be desired for imaging with 62Cu and PET.

Animals↗
PubMed2002

Biodistribution and toxicity studies of VSVG-pseudotyped lentiviral vector after intravenous administration in mice with the observation of in vivo transduction of bone marrow.

Lentiviral vectors can confer high levels of gene transfer and transgene expression in a variety of cell types. However, the biodistribution and toxicity after intravenous administration have not been reported. To address these issues of biodistribution and toxicity, an HIV-1-based vector, HR'cmvGFP, was administered to normal BALB/c mice by tail-vein injection. Nine different organs and bone marrow were evaluated by real-time quantitative PCR (QPCR) assay capable of a broad range of quantitation (5-log fold) to detect as few as one copy of the green fluorescent protein gene (GFP) per 10(5) cells. Four days after vector administration, high levels of transgene and gene expression were observed in liver, spleen, and bone marrow in all animals. By 40 days after injection, GFP levels had decreased in liver and spleen, but bone marrow exhibited a consistently high level of transgene. This finding was consistent with the increase in both GFP frequency and expression levels observed in peripheral blood by fluorescence-activated cell-sorting (FACS) analysis. Between 0 and 1% transgene was detected in all other organs. No significant pathologic lesions were found attributable to vector in any of the tissues examined. The observation of bone marrow transduction after intravenous vector administration suggests the possibility of an in vivo approach to stem cell gene therapy.

Animals↗
PubMed1989

The biodistribution of radiocopper-labeled compounds.

Porphyrins form extremely stable chelates with Cu2+. Two copper radionuclides, 67Cu and 64Cu, have attractive nuclear decay properties for use in nuclear medicine applications. We have investigated the use of radiocopper-labeled porphyrins for localization in inflamed tissue and for attachment to antibodies for tumor imaging and therapy. We have examined the biodistribution of a 67Cu labeled porphyrin, [5, 10, 15, 20-tetrakis(4-carboxyphenyl) porphinato [67Cu] copper (II)], 67 CuTCPP. The 67CuTCPP was intravenously injected into the tail vein of Fischer F344 male rats. The kidneys, liver, and spleen localize the greatest amounts of 67CuTCPP. The elimination of 67CuTCPP from the body is described by a normal exponential decay curve with a biological half-life of 108 hours and an effective half-life of 32 hours. We have also examined the biodistribution of 5-(4-carboxyphenyl)-10, 15,20-tris(4-sulfophenyl) porphinato [67Cu] copper (II) anti-Thy 1.2 antibody conjugates in normal and tumor-bearing male AKR/J mice. The liver, kidney, and tumor have the highest uptake of the 67Cu labeled antibody conjugate. In all 67Cu labeled compounds studied, the blood clearance was rapid and the bone concentration of the radiolabeled species was low.

Animals↗
PubMed1987

Comparisons of labeling efficiency, biological activity and biodistribution among 125I-, 67Ga-DTPA-and 67Ga-DFO-lectins.

The labeling efficiency, biological activity and biodistribution of 125I labeled and 67Ga chelating agent conjugated lectins were investigated. Pisum sativum agglutinin (PSA) and Lens culinaris agglutinin (LCH) were efficiently labeled with 67Ga using bifunctional chelating agents such as diethylenetriaminepentaacetic acid (DTPA) and deferoxamine (DFO), whereas labeling with 125I was significantly less efficient. The agglutinating activity of these lectins towards Ehrlich ascites tumor (EAT) cells was retained on conjugation with DFO, but not with DTPA. The in vitro binding ratio of 67Ga-DFO-lectins for EAT cells was almost the same as that of 125I-lectins. However, the value was significantly decreased in the case of 67Ga-DTPA-lectins. In the biodistribution study of radiolabeled lectins in Ehrlich solid tumor (EST) bearing mice, the accumulation of radioactivity in tumor tissue was very much less with 67Ga-DTPA-lectins than with 125I-lectins. However, the concentration was significantly elevated in the case of 67Ga-DFO-lectins. While, these lectins accumulated in liver, spleen, lung, and kidney to a greater extent than 67Ga citrate, the tumor to organ ratios became very low. These low tumor to organ ratios, in contrast to 67Ga citrate, will certainly inhibit the tumor delineation, and therefore it seems that in spite of a high accumulation ratio of 67Ga-DFO-lectins in tumor tissue, these agents are not useful in tumor detection.

Animals↗