Biomedical subjects

G E Meinken

Publications and source records attributed to G E Meinken.

At least 19 recordsLinked to original sources

PubMed1997

Tin-117m(4+)DTPA: pharmacokinetics and imaging characteristics in patients with metastatic bone pain.

UNLABELLED: Biokinetics and imaging characteristics of 117mSn(4+)DTPA have been studied in patients with metastatic bone pain. METHODS: Seventeen patients with bone pain due to metastasis were given three dose levels: 180 microCi/kg (6.66 MBq/kg), 229 microCi/kg (8.47 MBq/kg) and 285 microCi/kg (10.55 MBq/kg) body weight. Periodic blood and daily urine samples were collected for 14 days to measure percent injected activity retained in blood and that excreted in urine. Simultaneous anterior and posterior view whole-body images were obtained under identical scan settings at 1, 3.5 and 24 hr and on Days 3 and 7 and between 4-6 and 8-10 wk postinjection. The total body retention was calculated using the geometric mean counts. RESULTS: After intravenous injection, the total body clearance of 117mSn(4+)DTPA shows two components: a soft-tissue component and a bone component. The soft-tissue component accounts for 22.4% of the dose and consists of four subcomponents with an average biologic clearance half-time of 1.45 days (range 0.1-3.2 days). The bone component accounting for the remaining 77.6% of the dose shows no biologic clearance. A mean 22.4% of the dose is excreted in urine in 14 days; 11.4% within 24 hr. The uptake pattern appears similar to that of 99mTc-MDP. Peak uptake is observed in normal bone by 24 hr and metastatic lesions by 3-7 days. Pain palliation was observed with all three doses levels. CONCLUSION: Among the four potential bone pain palliation radionuclides, 117mSn(4+)DTPA demonstrates the highest bone uptake and retention. Some biokinetic and radionuclidic features of 117mSn(4+)DTPA are similar to other agents, but many features are different and unique and may make it an ideal bone pain palliation agent. Double-blind comparative studies are needed to determine its exact role in bone pain palliation.

Adult↗

PubMed1996

Pre-clinical and clinical studies of two new bifunctional chelating agents for immunoscintigraphy with 111In-anti-CEA monoclonal antibody.

Anti-CEA F(ab')2 monoclonal antibody fragments [F6 MAb F(ab')2] were conjugated to two bifunctional semi-rigid chelating agents derived from trans-1,2-diaminocyclohexane tetraacetic acid (CDTA), the monolithium salt of N-[methyl(2-isothiocyanatoethyl)carbamide] trans-1,2-diaminocyclohexane-N,N',N'-triacetic acid (SCN), and 4 isothiocyanato-trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (4-ICE) and labelled with 111In to obtain IIIIn-labelled-F6 MAb F(ab')2 conjugates (111In-F6-SCN and 111In-F6-4-ICE respectively). Biodistribution in mice and clinical studies were undertaken to assess the potential of these two ligands in the detection of colorectal adenocarcinoma recurrences and metastases in humans. Toxicity studies were carried out on guinea pigs and Swiss mice injected with a dose proportionally 100 times greater than that used in human studies. Clinical studies were performed in patients with clinically and/or biologically suspected adenocarcinoma recurrences. No immunoconjugate-induced toxicity was found. The biodistribution studies in mice gave better visualization of tumour sites with 111In-F6-SCN and 111In-F6-4-ICE than with 111In-F6-DTPA. Ten patients were included in the clinical protocol. 111In-F6-SCN and 111In-F6-4-ICE effectively visualized adenocarcinoma recurrences. However, in this small series, 111In-F6-4-ICE performed somewhat better than 111In-F6-SCN. The present study has demonstrated the potential of new bifunctional semi-rigid chelating agents coupled to antibody and labelled with 111In to localize recurrences (especially in liver) in humans using a one-step targeting method.

Adenocarcinoma↗

PubMed1995

Tin-117m(4+)-DTPA for palliation of pain from osseous metastases: a pilot study.

UNLABELLED: The physical and biological attributes of 117mSn(4+)-DTPA indicate that it should be an effective agent for palliative therapy of painful bony metastatic disease. The aim of this study was to evaluate whether or not this agent could effectively reduce pain while sparing the hemopoietic marrow from adverse effects. METHODS: Fifteen patients (10 males and 5 females) with painful bony metastases from various primary cancers were included in the study. Seven patients received 1.22 to 3.11 MBq/kg of 117mSn intravenously (Group 1) and eight patients received 4.85 to 5.77 MBq/kg (Group 2). All but one were treated as outpatients and followed for a minimum of 2 mo. RESULTS: In the first group, pain relief was non-assessable in four patients because of death or additional treatment of soft-tissue disease by another modality. One patient had no relief of pain, one had complete relief of pain and one had transient relief of pain. No myelotoxicity was observed. For Group 2, three patients achieved complete relief of pain, two good relief, two partial relief and one began to experience pain relief when he suffered a pathological fracture 2 mo post-treatment. None of these patients had myelotoxicity. CONCLUSION: Tin-117m(4+)-DTPA can reduce pain from metastatic disease to bone without inducing adverse reactions related to bone marrow. Further studies are needed to assess tolerance levels for the bone marrow and to evaluate response rates and duration of effect.

Bone Marrow↗

PubMed1993

Abscess scintigraphy with 99mTc-human immunoglobulin (IgG) using a one-step labeling method.

It was shown earlier that non-specific human gamma globulin (IgG) labeled with 111In can be used as an agent for abscess localization. We describe experimental results with 99mTc-IgG in animals bearing abscesses and tumors using a one-step labeling method with 99mTc. We studied this compound in several animal models: mice bearing turpentine abscesses and subcutaneously transplanted sarcomas, in rats with turpentine or E. coli abscesses and intracerebrally implanted gliomas and in rabbits with E. coli or turpentine abscesses. Blood clearance was studied in dogs. It was found that the absolute concentration of 111In-IgG in abscess and tumor was higher than that of 99mTc-IgG. However, the abscess-to-tumor ratio was higher for 99mTc-IgG. The 99mTc-IgG images were of high quality and abscesses could be detected as early as 30 min post-injection (p.i.). It appears that 99mTc-IgG has many potential advantages over 111In-IgG because of better physical properties of 99mTc, simpler preparation, lower cost and greater availability and the possibility of using higher 99mTc doses.

Abscess↗

PubMed1993

Introduction of five potentially metabolizable linking groups between 111In-cyclohexyl EDTA derivatives and F(ab')2 fragments of anti-carcinoembryonic antigen antibody--I. A new reproducible synthetic method.

The purpose of this study was to synthesize new bifunctional linker-chelating agents for the modification of the in vivo distribution of 111In-labeled antibodies. A general simple synthetic method of preparing cyclohexyl EDTA (CDTA) derivatives containing a linker/spacer group is described. Linkers prepared included a diester, a six carbon aliphatic chain, two thioethers and a disulfide group. The CDTA-linker compounds were coupled to F(Ab')2 fragments of anti-carcinoembryonic antigen monoclonal antibody and labeled with 111In with good retention of immunoreactivity.

Animals↗

PubMed1993

Introduction of five potentially metabolizable linking groups between 111In-cyclohexyl EDTA derivatives and F(ab')2 fragments of anti-carcinoembryonic antigen antibody--II. Comparative pharmacokinetics and biodistribution in human colorectal carcinoma-bearing nude mice.

The five linker-containing immunoconjugates described in the preceding paper were labeled with 111In and tested for their biodistribution, pharmacokinetics and immunoscintigraphic imaging properties in tumor-xenografted nude mice. The results were compared with DTPADA and CDTAMA for reference. Results showed that, for immunoscintigraphy, the derivatives in decreasing order of effectiveness were: aliphatic (tumor/liver > 4.5 and tumor/kidney > 6.5 at 96 h), thioether (tumor/liver > 3 and tumor/kidney > 1.2 at 24 h), ethylene glycol succinate (tumor/liver > 1.7 and tumor/kidney > 0.5 at 24 h) and disulfide (tumor/liver > 0.5 and tumor/kidney > 0.6 at 96 h). Pharmacokinetic results were complementary with those of the biodistribution studies and provide a basis for the study of in vivo metabolic mechanisms of linker-immunoconjugates. Indium-111-labeled linker-immunoconjugates appear promising for tumor imaging with better contrast than what is obtained with the use of the conventional 111In-DTPA dianhydride chelate.

Adenocarcinoma↗

PubMed1993

Biodistribution of Sn-117m(4+)DTPA for palliative therapy of painful osseous metastases.

Tin-117 has certain physical characteristics (half-life of 13.6 days, low-energy-conversion electrons, gamma photon of 158.6 keV) that suggest that it may be a favorable agent for radionuclide therapy. It has been shown in animal models that Sn-117m in the chemical form Sn(4+)diethylenetriaminepentaacetic acid localizes selectively in bone. The authors therefore studied its whole-body distribution in 10 patients to obtain absorbed dose estimates for therapy. The results showed that more than 50% of the administered activity was absorbed in the bones of patients with metastatic carcinoma. Retention was determined primarily by radioactive decay. For adult men, the radiation absorbed dose estimate averaged 54.8 mGy/MBq (203 rad/mCi) to bone surfaces and 6.1 mGy/MBq (22.6 rad/mCi) to the red marrow. All other tissues received less than 1/10 of the dose received by red marrow. These results suggest that a clinical therapeutic trial should be attempted.

Adult↗

PubMed1992

The use of a new radiopharmaceutical, 97Ru-DISIDA, and of 99Tcm-sulphur colloid for the simultaneous evaluation of duodenogastric reflux and gastric emptying.

There is no consensus or a uniform technique for measuring gastric emptying and numerous modalities have been reported. We report here the results obtained using a modification of the published techniques for the simultaneous measurement of duodenogastric reflux and gastric emptying utilizing simultaneously the recently developed radiopharmaceutical 97Ru-DISIDA, intravenously, and the oral administration of 99Tcm-sulphur colloid incorporated in a 'solid' test meal.

Administration, Oral↗

PubMed1990

Radioactive gold cluster immunoconjugates: potential agents for cancer therapy.

An 11 gold atom (undecagold) cluster was covalently attached to specific sites on Fab', F(ab')2 and whole IgG molecules such that each carried 11-33 gold atoms without significant loss of native immunospecificity. Gold cluster labeled 17-1A monoclonal F(ab')2 antibody fragments showed 80% immunoreactivity compared to native antibody fragments in binding to human colon carcinoma cells in vitro. Radioactive gold in vivo biodistributions in nude mice with human tumors are also reported. By using clusters, potentially a larger destructive payload can be carried per antibody.

Animals↗

PubMed1990

Recent developments in blood cell labeling research.

A number of recent developments in research on blood cell labeling techniques are presented. The discussion relates to three specific areas: 1) A new in vitro method for red blood cell labeling with 99mTc, 2) a method for labeling leukocytes and platelets with 99mTc, and 3) the use of monoclonal antibody technique for platelet labeling. The advantages and the pitfalls are examined in the light of available mechanistic information. Problems that remain to be resolved are reviewed. An assessment is made of the progress as well as prospects in blood cell labeling methodology including that using the monoclonal antibody approach.

Animals↗

PubMed1990

Development of a new radiolabel (203Pb) and new chelating agents for labeling monoclonal antibodies for imaging.

High liver uptake and slow body clearance presently limit the usefulness of 111In labeled antibodies for tumor imaging. We have investigated 203Pb as an alternative and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A, were labeled (bicyclic anhydride method) with 203Pb and 111In with 60 and 90 per cent labeling yields, respectively. The biodistribution of 203Pb-17-1A conjugates was compared with the corresponding 111In-labeled preparations and with 203Pb-DTPA, 203Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24 and 96 h. 203Pb labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared with indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2-diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium.

Animals↗

PubMed1990

Indium-111-labeled LDL: a potential agent for imaging atherosclerotic disease and lipoprotein biodistribution.

Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-(111In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-(125I) LDL binding to LDL receptors by 111In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of 111In-LDL by hypercholesterolemic rabbits was reduced by 86% compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of 111In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that 111In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.

Animals↗

PubMed1989

Synthesis and biological properties of the lipophilic technetium-99m complex 99mTc(acac)3.

In the development of technetium-99m radiopharmaceuticals for the evaluation of regional cerebral perfusion, one series of complexes that has remained unexplored is the neutral lipophilic tris complexes formed with beta-diketonato ligands. The prototype complex of this series, tris(2,4-pentanedionato) technetium(III), has been prepared via a new synthetic route and chemically characterized using 99Tc and the biodistribution of the no-carrier-added 99mTc complex has been determined. The 99mTc complex was found to be distributed throughout the body with persistent high blood levels indicative of a high degree of protein binding. The primary route of excretion was the hepatobiliary system as indicated by the appearance of 99mTc in the gut and feces at longer sample times post-injection. Although this complex was not retained by the brain, it does provide a starting point from which a more effective agent might be developed.

Animals↗

PubMed1989

A new cholescintigraphic agent: ruthenium-97-DISIDA.

These are the first human experiments with 97Ru-DISIDA, a potentially new alternative to 131I-rose bengal where delayed imaging is indicated. 97Ru has a convenient half life. A DISIDA labeling kit was utilized to prepare the radiotracer for 17 patients (age 6 weeks-84 years). The cholescintigraphic data correlated well with other imaging procedures and with clinical findings. Dosimetric calculations were carried out and were compared with the radiation burden associated with the use of 99mTc-DISIDA and 131I-rose bengal.

Biliary Tract Diseases↗

PubMed1989

Comparative dual-tracer studies of carbon-14 tryptophan and iodine-131 HIPDM in animal models of pancreatic diseases.

Our previous studies have shown that a significant amount of the diamine derivative 131I-N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) is taken up and retained by the normal pancreas. Therefore, we studied the uptake of [131I]HIPDM in various pathophysiological models in mice (chronic alcoholism, diabetes with beta-cell atrophy and obesity with beta-cell hypertrophy) and compared to 14C-L-Tryptophan (TRY) distribution in order to determine the factors influencing their pancreatic uptake. In normal animals, the pancreas uptake of TRY was generally higher than HIPDM. In diabetes, the relative concentration of both compounds was higher over the controls; however, in obesity, TRY showed lower accumulation than in controls while HIPDM showed no significant difference. Chronic ethanol (20%) ingestion increased TRY uptake in the pancreas compared to controls (36.88 +/- 3.21 vs. 30.03 +/- 4.17% ID/g; p less than 0.01) after 5 wk study period, but it decreased by 10 wk (22.36 +/- 0.95% ID/g; p less than 0.005). There were no significant changes in [131I]HIPDM distribution in alcoholics as compared to the controls. Radioiodinated HIPDM has potential advantages over [11C]TRY for pancreatic imaging since conventional imaging techniques can be employed. Our data, however, suggest that 11C-L-TRY is a more sensitive indicator of various pancreatic disorders.

Animals↗

PubMed1986

Radioimmunodetection of human tumor xenografts by monoclonal antibody F(ab')2 fragments.

Experimental procedures are described for the radiolocalization of human tumors by murine monoclonal antibodies (MAb) in animal model systems. Visualization of tumor xenografts was clearer in nude mice as compared to experimentally immunosuppressed mice due to the higher viability of the tumors in nude mice. MAb localization in tumor tissue was greatly enhanced when F(ab')2 fragments rather than intact antibody molecules were used. Although tumors could be visualized with either 131I-, 123I- or 111In-labeled MAb fragments without using background subtraction, tumor-to-background ratios of radioactivity were highest for 131I-labeled fragments. 131I-labeled F(ab')2 fragments of eight MAb against human colorectal carcinoma, melanoma or lung carcinoma localized specifically only in those tumors that bound the MAb in vitro and not in unrelated tumors. Radiolabeled fragments of MAb with other specificities (anti-hepatitis virus MAb) did not localize in tumors. All MAb that inhibited tumor growth in nude mice effectively localized these tumors by gamma-scintigraphy. On the other hand, some MAb were effective in localizing tumors but ineffective in inhibiting their growth. The ability of the specific radiolabeled F(ab')2 fragments to localize in tumor grafts correlated significantly with MAb binding affinity and density of antigenic sites on tumor cells together, but not with either in vitro binding parameter alone. Thus, Scatchard analysis of MAb binding to tumor cells may be an effective means to screen for MAb with tumor radiolocalization potential.

Animals↗

PubMed1986

Dual tracer autoradiographic study of beta-methyl-(1-14C) heptadecanoic acid and 15-p-(131I)-iodophenyl-beta-methylpentadecanoic acid in normotensive and hypertensive rats.

The myocardial distribution of 15-p-[131I]iodophenyl-3-(R,S)-methylpentadecanoic acid (BMPDA) and 1[14C]-3-(R,S)-methylheptadecanoic acid (BMHDA) was compared in normotensive and hypertensive rats using quantitative dual tracer autoradiographic techniques. The myocardial distribution of carbon-14 [14C] BMHDA and iodine-131 [131I] BMPDA was nearly homogeneous in the normotensive rats, while both tracers showed similar, though very heterogeneous, distribution in hypertensive hearts with decreased uptake in the endocardial region. Our data demonstrate that myocardial distribution of [131I]BMPDA was essentially the same as [14C]BMHDA, and thus single photon emission computed tomographic imaging with 123I-labeled BMPDA could be useful for the detection of regional changes of myocardial fatty acid uptake in patients with prolonged and severe hypertension.

Animals↗

PubMed1985

The development and in-vivo behavior of tin containing radiopharmaceuticals--I. Chemistry, preparation, and biodistribution in small animals.

Tin is an essential ingredient of most technetium-99m radiopharmaceutical preparations but its in-vivo distribution and long-term fate are not well understood. Tin-117m (t1/2 14d; gamma 159 keV, 86%) is an ideal tracer for studying biological behavior of tin compounds as well as for developing clinically-useful radiopharmaceuticals. This work describes the preparation and in-vivo distribution in mice of a number of tin-117m labeled compounds with commonly used ligands. High bone uptake of most compounds studied as well as the unexpectedly high bone uptake of Sn4+-DTPA indicates a high bone affinity of tin bound to chemically diverse ligands. Various compounds show subtle but significant differences in blood clearance, excretion, and soft-tissue uptake. Differences among Sn2+ and Sn4+ compounds with the same ligand are particularly noteworthy. For stannic chelates, higher bone uptake, faster blood clearance, and reduced soft-tissue concentration were observed. It appears that tin compounds bind to bone predominantly through the tin atom and that the differences in biodistribution depend on factors such as the net charge on the complex, the oxidation state of tin, and hydrolytic and kinetic stabilities of the complexes. The results indicate that the favorable half-life and decay characteristics of tin-117m in various stannic compounds, especially stannic-DTPA, make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

Animals↗