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PubMed2007

Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice.

PURPOSE: Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. METHODS: Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with (99m)Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. RESULTS: The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. CONCLUSION: A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We believe that the approach described herein may be applied to any of the alternative pretargeting approaches and animal tumor models currently under investigation. Furthermore, appreciation of the concepts may provide a rationale for selecting dosages and timings in human pretargeting studies as an alternative to pure empirical means.

Algorithms↗

PubMed1995

Repeating the avidin "chase" markedly improved the biodistribution of radiolabelled biotinylated antibodies and promoted the excretion of additional background radioactivity.

Immunoscintigraphy using radiolabelled biotinylated monoclonal antibodies followed by infusion of avidin as a "chase" has been recently reported to improve the biodistribution for both immunoscintigraphy and radioimmunotherapy. In this study the circulating protein-bound and avidin-binding fractions of radiolabelled biotinylated antibodies were determined serially after injection of an avidin "chase", and the effect of repeating the avidin chase was also studied. Nude mice bearing KT005 human osteogenic sarcoma were injected with radiolabelled biotinylated antitumour monoclonal antibody (OST7). After injection of an avidin chase, the protein-bound and avidin-binding fractions in plasma were determined serially using the trichloroacetate method and avidin-Sepharose gel. The biodistribution of radiolabelled biotinylated OST7 was compared after single and double avidin chases with no chase. At 6 h after the first avidin chase in mice injected with radioiodinated and technetium-labelled biotinylated OST7, 67.7% and 67.8%, respectively, of the plasma radioactivity was available for binding to avidin and was cleared from the circulation. Reinjection of avidin decreased the plasma radioactivity and improved the biodistribution of the radiolabelled biotinylated antibodies. Repeating the avidin chase markedly improved the biodistribution of the radioiodine-labelled biotinylated antibody when compared with the use of a single avidin chase. This new method for radioimmunotherapy is sure to protect the critical organs from radiation injury without decreasing the therapeutic effect.

Animals↗

PubMed1996

Modification of antibody isoelectric point affects biodistribution of 111-indium-labeled antibody.

We evaluated the influence of changes in charge on the biodistribution of 111In-labeled purified rabbit antihuman serum albumin (R-HSA) IgG conjugated to diethylenetriaminepentaacetic dianhydride (DTPA). Optimization of isoelectric point (pI) may influence the biodistribution profile, especially retention in vital organs, which ultimately affects radioimmunoimaging. Experiments were designed to modify the pI of R-HSA by conjugating various molar ratios of DTPA (DTPA:R-HSA ratios 5:1 to 100:1). The pI of the conjugates was determined by isoelectricfocusing (IEF). 111In-labeled DTPA:R-HSA with known pI range was injected intraperitoneally into BALB/c mice to evaluate biodistribution. There was a proportional relationship between the molar ratio of DTPA to R-HSA IgG and the number of DTPA substituted. Molar ratios of 5, 10, 20, 50 and 100 gave, on average, 2.0, 3.6, 5.1, 9.5 and 16.0 DTPA per R-HSA IgG, respectively. An anodal shift in the pI of 111In-labeled R-HSA IgG was noted with increased number of DTPA conjugation. Biodistribution studies at both 4 and 24 h showed sequential increase in the liver activity with increasing number of DTPA per antibody, whereas colon and small intestine showed a decrease in the activity at 4 h. The organ-specific increase (e.g., liver) or decrease (e.g., colon and small intestine) in the activity may depend on a critical balance of charge of a particular organ and its interaction with the amount of negative charge carried by the antibody conjugate. The results suggest that pI optimized 111In-labeled antibody could be used to increase or decrease colon and hepatic retention for more efficient radioimmunoimaging of colon tumors and their hepatic metastasis.

Animals↗

PubMed2000

Characteristics and biodistribution of cationic liposomes and their DNA complexes.

We have developed some novel liposome formulations for gene transfection. The formulations consisting of O,O'-ditetradecanoyl-N-(alpha-trimethyl ammonio acetyl) diethanolamine chloride (DC-6-14) as a cationic lipid, phospholipid and cholesterol showed effective gene transfection activity in cultured cells with serum and in vivo, i.e., intraperitoneal injection in mice. In this report, the physicochemical characteristics and biodistribution of the liposomes containing DC-6-14 (DC-6-14 liposomes) as a drug (gene) carrier for gene therapy were investigated in vitro and in vivo. DC-6-14 liposome-DNA complexes were usually thought to have positive surface charge. However, depending on the ratio of DNA to liposomes, zeta-potential of the complexes became negative. The diameter of the complexes also depended on the DNA-liposome ratio, and showed a maximum when their surface potential was neutral. When biodistribution of the complexes was determined after intravenous injection, positively charged complexes showed an immediate lung accumulation. On the other hand, negatively charged complexes did not show lung accumulation. These results have suggested that biodistribution of the DNA-liposome complexes, prepared with DC-6-14 liposomes, depends on their surface charge. Therefore, some surface modification of DC-6-14 liposomes may improve the biodistribution and hence the targetability of their DNA complexes.

Animals↗

PubMed2004

Biodistribution of filamentous phage peptide libraries in mice.

In vivo phage display is a new approach to acquire peptide molecules that bind stably to a given target. Phage peptide display libraries have been selected in mice and humans and numerous vasculature-targeting peptides have been reported. However, in vivo phage display has not typically produced molecules that extravasate to target specific organ or tumor antigens. Phage selections in animals have been performed for very short times without optimization for biodistribution or clearance rates to a particular organ. It is hypothesized that peptides that home to a desired antigen/organ can be obtained from in vivo phage experiments by optimization of incubation times, phage extraction and propagation procedures. To accomplish this goal, one must first gain a better understanding of the in vivo biodistribution and rate of clearance of engineered phage peptide display libraries. While the fate of wild type phage in rodents has been reported, the in vivo biodistribution of the commonly used engineered fd-tet M13 phage peptide display libraries (such as in the fUSE5 vector system) have not been well established. Here we report the biodistribution and clearance properties of fd-tet fifteen amino acid random peptide display libraries in fUSE5 phage in three common mouse models employed for drug discovery - CF-1, nude, and SCID mice.

Animals↗

PubMed1994

Comparative biodistributions of indium-111-labelled macrocycle chimeric B72.3 antibody conjugates in tumour-bearing mice.

A novel 111In ligand (a C-functionalised derivative of 1,4,7-triazacyclononanetriacetic acid), termed 9N3, was covalently attached to chimeric B72.3, labelled with 111In and compared with 111In-labelled chimeric B72.3 diethylenetriaminepentaacetic acid (DTPA) cyclic anhydride conjugate (cDTPA) and a C-linked derivative of DTPA (CT-DTPA) in athymic mice bearing human colon carcinoma xenografts. Significant differences in biodistribution were observed between 9N3 and cDTPA conjugates especially in the tumour uptake and blood, liver, femur and colon levels at 24, 48 and 144 h. Significantly higher tumour uptake was observed for 111In-cB72.3-9N3 compared with 111In-cB72.3-cDTPA at all time points. Radiolocalisation (RI) indices increased with time for the 9N3 conjugate but remained constant for the cDTPA conjugate. The biodistribution of 111In-labelled cB72.3-CT-DTPA was similar to that of 111In-labelled cB72.3-9N3 except for elevated kidney levels. A 12N4 macrocycle (a C-functionalised derivative of 1,4,7,10-tetraazacyclododecanetetraacetic acid) was also tested for its ability to chelate 111In and its biodistribution examined. Labelled conjugates with this macrocycle were more difficult to prepare in a stable form but gave a very similar biodistribution to the 9N3 macrocycle conjugate. Macrocycle-antibody conjugates of this type offer considerable promise for tumour imaging in patients.

Amines↗

PubMed1991

In vivo biodistribution of a radiolabeled blood substitute: 99mTc-labeled liposome-encapsulated hemoglobin in an anesthetized rabbit.

Liposome-encapsulated hemoglobin (LEH) is an erythrocyte substitute that is a potential resuscitative fluid for the in vivo delivery of oxygen. We have noninvasively imaged radiolabeled LEH in vivo with technetium-99m (99mTc) to study the biodistribution in an anesthetized rabbit. Rabbits (2.5 kg, n = 8) were infused with 30 ml of LEH (200 mg of phospholipid, 2.5 g of hemoglobin per kg of body weight) and imaged with a gamma camera continuously for 2 hr. At 20 hr postinfusion, the animals were imaged again and sacrificed; the organs were weighted and their radioactivity was determined for autopsy organ distribution. Organ uptake from the images was corrected for organ-associated blood pool, which was determined by infusion of 99mTc-labeled rabbit erythrocytes. Blood pool and decay-corrected biodistribution data reveal the kinetics of LEH distribution, with an initial rapid uptake by the liver, 8% at 30 min and 15% at 2 hr. The spleen accumulates less LEH initially, 3% at 30 min and 7% at 2 hr, with an apparent linear uptake of LEH over this time period. Image biodistribution data was also validated at 20 hr by tissue sampling. At 20 hr postinfusion, autopsy biodistribution data reveals approximately 42.6% of the total counts remaining in the blood, 15.4% in the liver, 18.1% in spleen, 3.2% in the lungs, 2.4% in muscle, 1.6% in urine, and trace levels in the kidney, brain, and heart (less than 1%). There is no evidence of hemoglobin release from LEH or kidney dysfunction (normal creatinine and blood urea nitrogen) at any time over the course of the study.

Alanine Transaminase↗

PubMed2003

Preparation, characterisation and biodistribution of 99mTc-labeled liposome encapsulated cyclosporine.

The present study investigated the effect of charge (neutral, negative and positive) on liposomal membrane on the distribution of cyclosporine encapsulated in it to various organs. Liposomes were prepared by using different phospholipids by thin film hydration followed by sequential extrusion through polycarbonate membranes to achieve a desired particle size, with high entrapment efficiency and then lyophilised using sucrose as cryoprotectant. The possible in vivo distribution of cyclosporine and its liposomes after direct labeling with reduced technetium-99m has been studied in mice. The blood kinetics and biodistribution study of these labeled complexes shows prolonged circulation of positive and neutral charged liposomes in blood compared to free drug and negative charged liposomal formulation. The biodistribution of the tagged liposomes confirms that increased radioactivity was seen in liver and spleen, with minimal involvement of the kidney. At 4 h post injection the biodistribution data in kidney reveals approximately 1-2% of the injected dose was present for cyclosporine loaded liposomes, which elicits the possibility of reducing the nephrotoxicity, generally seen in free cyclosporine. Interestingly, the biodistribution and gamma imaging studies of the charged cyclosporine liposomes indicated that an appreciable amount of these labeled complexes goes to bone marrow when compared to the free cyclosporine. The findings demonstrate the distribution of these liposomes within various organs and proved that the positively charged liposomes experience increased bone uptake and prolonged circulation half-life. Hence this finding implies the possibility of using these formulations for liver and bone marrow transplantation.

Animals↗

PubMed1999

Intrapatient consistency of imaging biodistributions and their application to predicting therapeutic doses in a phase I clinical study of 90Y-based radioimmunotherapy.

Intrapatient variation in the biodistribution of the chimeric monoclonal antibody cT84.66 was assessed in 19 patients having a variety of carcinoembryonic antigen (CEA) positive tumors. The two studies, including whole-body imaging and blood and urine specimen collections, were conducted within 14 days of each other using (111)In-cT84.66 at a fixed total protein dose of 5 mg per patient per study. An initial pretherapy infusion of (111)In-cT84.66 was administered followed by a therapy coinfusion of (111)In-ct84.66 and 90Y-cT84.66 A closed five-compartment model was used to integrate source organ activity curves as residence time inputs into the MIRDOSE3 program. Normal organ absorbed doses were estimated for 90Y-cT84.66, the corresponding radiotherapeutic agent. For the two (111)In-cT84.66 biodistributions, all data were modeled with a R2 value of between 0.72 and 1.00 with the exception of the urine data taken during therapy. This was due to the need of diethylenetriaminepentaacetic acid during the therapy phase because of the possibility that yttrium might escape from the chelator attached to the antibody. With the assurance that the biodistributions were reproducible, we were able to estimate the 90Y-cT84.66 absorbed doses on a per-patient basis. Concordance coefficients showing the agreement between the imaging and therapy phase dose estimates were between the 0.60 and 0.99 levels for liver, spleen, red marrow, total body, and other organ systems. Median results were: 27, 17, and 2.7 rad/mCi of 90Y-cT84.66 for liver, spleen, and red marrow, respectively. Because of decreases in platelets and white cells as the amount of 90Y was increased, dose-limiting toxicity was found at 22 mCi/m2. We conclude that patient biodistributions were consistent over time to 14 days so as to allow absorbed dose estimation in a radioimmunotherapy trial involving the cT84.66 anti-CEA antibody.

Adult↗

PubMed2006

Host factors that impact the biodistribution and persistence of multipotent adult progenitor cells.

Multipotent adult progenitor cells (MAPCs) are marrow-derived pluripotent stem cells with a broad differentiation potential. We sought to identify factors that affect adoptively transferred MAPCs. In vitro, MAPCs expressed low levels of major histocompatibility complex (MHC) antigens, failed to stimulate CD4(+) and CD8(+) T-cell alloresponses, and were targets of NK cytolysis. To study in vivo biodistribution, we labeled MAPCs with luciferase for sequential quantification of bioluminescence and DsRed2 for immunohistochemical analysis. C57BL /6 MAPCs were infused intravenously into C57BL /6, Rag-2(-/-) (T- and B-cell-deficient), and Rag-2(-/-)/IL-2Rgamma(c)(-/-) (T-, B-, and NK-cell-deficient) mice. In C57BL /6 mice, MAPCs were transiently detected only in the chest compared with long-term persistence in T- and B-cell-deficient mice. NK depletion reduced MAPC elimination. Because the lungs were the major uptake site after intravenous injection, intra-arterial injections were tested and found to result in more widespread biodistribution. Widespread MAPC biodistribution and long-term persistence were seen in irradiated recipients given allogeneic marrow and MAPCs; such MAPCs expressed MHC class I antigens in tissues. Our data indicate that the biodistribution and persistence of reporter gene-labeled MAPCs are maximized after intra-arterial delivery or host irradiation and that T cells, B cells, and NK cells contribute to in vivo MAPC rejection.

Animals↗

PubMed1992

Biodistribution studies of liposome encapsulated hemoglobin (LEH) studied with a newly developed 99m-technetium liposome label.

A new method has been developed to label preformed liposomes with 99m-Technetium (99mTc) using hexamethylpropylenamine oxime (HMPAO). 99mTc is an ideal isotope for performing non-invasive dynamic biodistribution studies. This labeling method results in a high labeling efficiency (greater than 95%) and is stable as determined by both in vitro and in vivo studies. In vitro studies indicated that glutathione encapsulated in the LEH is important in the labeling process with 99mTc-HMPAO. In vivo studies with LEH were performed on 7 rabbits with dynamic scintigraphic 1 minute images performed from 1-120 minutes. Delayed images were performed at 20 hours followed by sacrifice and organ counting. Dynamic images reveal a gradual deposition of the LEH in the liver and spleen. Twenty hour biodistributions revealed 50% of the LEH remaining in the blood, 15% in the liver, 14% in the spleen, 3% in lungs, 3% in muscle with trace amounts in the brain, kidneys, and heart. Doses per gram were highest in the spleen with 12.5% of the injected dose per gram of spleen vs. 0.2% per gram of liver. This labeling technique is an effective method for non-invasively monitoring dynamic changes in liposome biodistribution and can be used to study the effects of various liposome modifications on biodistribution.

Animals↗

PubMed2002

Alteration of 99mTc-DMSA biodistribution in glomerulonephritis.

BACKGROUND: The aim of this study was to assess the relation between (99m)Tc-DMSA biodistribution and its reliability as a marker of renal function in patients with glomerular kidney diseases. MATERIAL AND METHODS: Sixty-seven patients involved in this study were classified into two groups according to (99m)Tc-DTPA clearance and serum creatinine values: the 1st group consisted of 42 patients without renal failure while the 2nd group included 25 patients with renal failure. (99m)Tc-DMSA biodistribution was determined by measuring kidney, blood and urine activity at 2 h and 4 h. RESULTS: The results, compared with those of 23 healthy volunteers, indicated the quantitative alteration of (99m)Tc-DMSA distribution in both glomerulonephritis patient groups. In reference to the control mean values of 2 h and 4 h, in patients without renal failure, kidney activity was found decreased to 52% and 57%, while the blood activity increase of 37% and 44% was recorded together with the urine activity increase of 38% and 23%. In patients with renal failure the alterations of renal and blood activity were more remarkable, but the urine loss was found to be unchanged. CONCLUSIONS: It is suggested that these biodistribution changes originate mainly from tubular impairment. However, in glomerulonephritis patients, altered glomerular filtration might considerably affect biodistribution of this radiopharmaceutical and limits its suitability for precise quantitative estimation of renal function.

Journal Article↗

PubMed2005

(89)Zr as a PET surrogate radioisotope for scouting biodistribution of the therapeutic radiometals (90)Y and (177)Lu in tumor-bearing nude mice after coupling to the internalizing antibody cetuximab.

UNLABELLED: Immuno-PET as a scouting procedure before radioimmunotherapy (RIT) aims at confirming tumor targeting and accurately estimating radiation dose delivery to both tumor and normal tissues and might therefore be of value for selection of patient candidates for RIT. A prerequisite for this approach is that PET radioimmunoconjugates and RIT radioimmunoconjugates must show a similar biodistribution. In the present study, we evaluated the potential of the long-lived positron emitter (89)Zr to predict biodistribution of the residualizing therapeutic radiometals (88)Y (as a substitute for (90)Y) and (177)Lu when labeled to the monoclonal antibody (mAb) cetuximab via different types of chelates. Cetuximab was selected as a model mAb because it abundantly internalizes after binding to the epidermal growth factor receptor. METHODS: Cetuximab was labeled with (89)Zr using succinylated desferrioxamine B (N-sucDf). The chelates p-benzyl isothiocyanate-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (p-SCN-Bz-DOTA) and p-isothiocyanatobenzyl diethylenetriaminepentaacetic acid (p-SCN-Bz-DTPA) were both used for radiolabeling with (88)Y and (177)Lu. For measurement of the in vitro stability of each of the 5 radioimmunoconjugates, samples were incubated in freshly prepared human serum at 37 degrees C up to 16 d. Biodistribution was assessed at 24, 48, 72, and 144 h after intraperitoneal coinjection of the PET and RIT conjugates in nude mice bearing the squamous cell carcinoma xenograft line A431. RESULTS: Cetuximab premodification with N-sucDf, p-SCN-Bz-DOTA, or p-SCN-Bz-DTPA resulted in chelate-to-mAb molar ratios of about 1. After radiolabeling and purification, the radiochemical purity and immunoreactive fraction of the conjugates always exceeded 97% and 93%, respectively. All conjugates were stable in serum, showing a radioactivity release of less than 5% until day 7. From day 7 until day 16, an enhanced release was observed for the (89)Zr-N-sucDf, (88)Y-p-SCN-Bz-DTPA, and (177)Lu-p-SCN-Bz-DTPA conjugates. The coinjected PET and RIT conjugates showed similar biodistributions, except for the thighbone and sternum. For example, the (89)Zr-N-sucDf conjugate showed a 2.0-2.5 times higher radioactivity accretion in the thighbone than did the RIT conjugates at 72 h after injection. CONCLUSION: In view of the advantages of PET over SPECT, (89)Zr-immuno-PET is a promising modality for in vivo scouting of (90)Y- and (177)Lu-labeled mAbs, although care should be taken when estimating bone marrow doses.

Animals↗

PubMed2006

Collimator selection, acquisition speed, and visual assessment of 131I-tositumomab biodistribution in a phantom model.

UNLABELLED: (131)I-Tositumomab has been used in treating patients with non-Hodgkin's lymphoma. It is generally recommended that high-energy collimators be used to image patients before they receive (131)I-tositumomab therapy, to determine the effective half-life for therapeutic dose and gross biodistribution. Because many nuclear medicine departments do not possess high-energy collimators, this study was designed to assess the suitability of using medium-energy collimators. The effect of scanning speed was also investigated, in an attempt to optimize the acquisition time. METHODS: Measurements were taken using an elliptic anthropomorphic torso phantom and an organ-scanning phantom fitted with fillable spheres (1-5 cm in diameter) and organ inserts. Three phantom studies were performed with differing initial (131)I concentrations in the organs, the spheres, and the thoracic and abdominal chambers. Images were acquired with both high-energy and medium-energy collimators and at acquisition speeds of 20 and 100 cm/min. The half-life for each combination (study/collimator/speed) was calculated from a linear fit of the data. The contrast of the tumor sphere was assessed using 2 identical regions, placed on and beside the sphere, and averaged over several time points. Biodistribution and image quality were visually assessed by 2 independent observers. RESULTS: Measured half-life values and visual assessment of biodistribution showed no significant difference between the 2 collimators (P = 0.32) or acquisition speeds (P = 0.85). A significant difference in the contrast of the tumor spheres was observed between the 2 collimators (P < 0.01) but not between acquisition speeds. Visual assessment of the images showed increased noise on the image acquired at 100 cm/min, although this noise did not affect lesion detectability. CONCLUSION: Measured half-life is not significantly different between the 2 collimators; hence, calculation of the residence time would be nearly the same. Medium-energy collimators can be used to accurately calculate the (131)I-tositumomab therapeutic dose and detect alterations in biodistribution.

Antibodies, Monoclonal↗

PubMed1990

Human biodistribution of 111In-labeled B72.3 monoclonal antibody.

The murine IgG1 monoclonal antibody B72.3 reacts with human colorectal, breast, lung, pancreatic, gastric, and ovarian tumors. Human biodistribution studies using intact 131I-B72.3 have been reported by Carrasquillo et al. (J. Nucl. Med., 29: 1022-1030, 1988). We have performed similar studies on five patients using i.v. infusion of 20 mg of intact 111In-B72.3 (Cytogen Corp.). Serum clearance is similar with a t1/2 of 64.2 h (range, 44-80) for 111In-B72.3 and 65 h (range, 32-106) for 131I-B72.3 (J. A. Carrasquillo et al., J. Nucl. Med., 29: 1022-1030, 1988). However, organ biodistribution is markedly different. For 131I-B72.3, hepatic and splenic clearance mirrors blood pool clearance (J. A. Carrasquillo et al., J. Nucl, Med., 29: 1022-1030, 1988). For 111In-B72.3, there is rapid uptake in tumor, liver, spleen, kidney, lumbar spine, and testes by 2-6 h with no significant clearance over the next 9 days. For 111In-B72.3, quantitative analysis of liver (from biopsy specimens), spleen, kidney, and lumbar spine (from scintiphoto regions of interest after background subtraction and attenuation correction) shows the following peak organ biodistributions in percentage infused dose: liver, 32%; spleen, 3.9%; kidneys, 3.5%; and lumbar vertebral bodies (marrow sample), 2.7%. For both 111In-B72.3 and 131I-B72.3, the principal route of excretion from the body is urinary with excretion rate of 131I faster than 111In. The marked differences between 111In-B72.3 and 131I-B72.3 biodistribution and clearance strongly influence the dosimetry, immunodetection, and immunotherapeutic potentials of B72.3 MoAb.

Aged↗

PubMed1982

Effects of concurrent drug therapy on technetium Tc-99m gluceptate biodistribution.

Drug interactions with technetium Tc-99m gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium Tc-99m gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium Tc-99m gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium Tc-99m gluceptate.

Acetaminophen↗

PubMed1993

Biodistribution of a benzoporphyrin derivative-monoclonal antibody conjugate in A549-tumor-bearing nude mice.

Biodistribution of the photosensitizer benzoporphyrin derivative monoacid ring A (BPD) was compared in DBA/2 mice bearing the syngeneic M-1 tumor and nude mice bearing the A549 human squamous cell carcinoma. These studies, using internally labeled 14C-BPD showed that in general, biodistribution between the two strains was equivalent with the exception of two tissues; lymph nodes (BPD levels were higher in nude mice) and tumor (BPD levels were lower in nude mice). Further studies were carried out in A549-tumor-bearing nude mice in which the biodistribution of BPD conjugated to a monoclonal antibody (5E8) with specificity for an antigen on A549 cells was compared to a conjugate prepared with an irrelevant monoclonal antibody (T48). These studies showed that both conjugates had biodistribution characteristics which distinguished them from free BPD in that they remained in the circulation and most tissues for significantly longer times than did free BPD. Also, with the exception of the 5E8-BPD conjugate and A549 tumor tissue, levels in all tissues were highest at the 3-h time point following injection of conjugates. In the case of A549 tumor and the 5E8-BPD conjugate the highest concentration of 14C-labeled material was observed at the 14-h time point following injection. The results reported herein show that the conjugates tested behaved differently from free BPD, indicating that the materials did not become dissociated in vivo and that the specific conjugate (5E8-BPD) demonstrated specificity for the A549 tumor in terms of the kinetics of its accumulation in tumor tissue.

Animals↗

PubMed1996

Biodistribution and dosimetry of technetium-99m-hydrazino nicotinamide IgG: comparison with indium-111-DTPA-IgG.

UNLABELLED: The biological behavior of human polyclonal immunoglobulin G (IgG), radiolabeled with 99mTc via a nicotinyl hydrazine derivative (99mTc-HYNIC-IgG), was evaluated in normal human subjects. METHODS: Initial biodistribution and dosimetry studies were performed in six normal male volunteers. Additionally, 99mTc-IgG and 111In-DTPA-IgG were co-injected into six subjects and scintillation camera images were acquired at 6 and 18 hr later and serial blood and urine samples were collected. Biodistribution of both radiopharmaceuticals were measured by region of interest analysis. In the dual-injection group, images were crossover-corrected. RESULTS: All subjects tolerated injection of the radiolabeled IgG preparations without apparent ill effects. Biodistribution of the two antibody preparations were remarkably similar with an increase in liver and abdominal activity for the 111In preparation. Linear correlation of the tissue-to-blood ratios of 99mTc and 111In-labeled IgG was observed at both times (r2 > 0.98). The slopes of the regression line were 0.97 and 0.76 at 6 and 18 hr, respectively. The beta phase of the blood clearance of 99mTc-HYNIC-IgG was significantly delayed (p < 0.01) compared with 111In-IgG (t1/2: 51.9 +/- 6.5 versus 35.3 +/- 3.4 hr). In contrast, the volumes of redistribution and urinary excretions of the radiopharmaceuticals were not significantly different. CONCLUSION: These studies establish that the biodistribution of 99mTc-HYNIC-IgG in normal human subjects is nearly identical to 111In-DTPA-IgG.

Adult↗