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Biomedical subjects

M Blau

Publications and source records attributed to M Blau.

At least 37 records · Page 2Linked to original sources
PubMed1987

Technetium-99m bis (aminoethanethiol) complexes with amine sidechains--potential brain perfusion imaging agents for SPECT.

In an effort to develop new clinically useful technetium-99m bis(aminoethanethiol) ([99mTc]BAT) complexes for the evaluation of regional cerebral perfusion, two new BAT ligands containing amines in the sidechain were synthesized and subsequently complexed with 99mTc to yield the target complexes: [99mTc]DEA and [99mTc]TMPDA. Each complex was obtained as mixtures of two isomers, syn and anti, which were separated chromatographically. In biodistribution studies, both isomers of [99mTc]TMPDA showed little uptake in the brain. In contrast, the brain uptake values at 2 and 15 min for [99mTc]DEA-anti were 0.99 and 0.26, whereas, the corresponding values for DEA-syn were 2.27, 0.64% dose/organ, respectively. Autoradiographic studies (in rats) using both isomers of [99mTc]DEA show a fixed regional distribution and a higher concentration of radioactivity in the gray matter relative to the white matter. Planar imaging using [99mTc]DEA-syn clearly demonstrates localization of the complex in the brain with a T 1/2 of 41 min, suggesting some potential for use with single photon emission computed tomography.

Animals↗
PubMed1987

Temporal evolution of brain distribution of IMP and HIPDM. Concise communication.

Early and late brain distribution of iodine-labelled N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM) and iodine labelled N-isopropyl-p-iodoamphetamine (IMP) were compared in rat and one human patient with a recent stroke in the right middle cerebral artery area. In rat, an important 'redistribution' of cerebral activity was observed in various areas of the brain, mainly white matter, whereas no such observation was made with HIPDM. In the patient, the right area was hypoactive during the early SPECT with IMP and HIPDM, and redistribution was observed in the late SPECT only with IMP. We suggest that while HIPDM appears to reflect regional cerebral perfusion, IMP distribution is dependent upon metabolic brain activity.

Aged↗
PubMed1985

Radiotracers for functional brain imaging.

The rapid growth of nuclear medicine 25 years ago was in large part related to the success of brain tumor imaging using radiopharmaceuticals designed to detect changes in the blood-brain barrier (BBB). The success of computed tomography, and more recently nuclear magnetic resonance, in imaging these lesions has all but eliminated the use of radioactive agents for brain tumor detection. But, in recent years there has been a new wave of interest in isotope studies of the brain. The recent emphasis has been on agents which enter the brain across the BBB and are designed to provide functional data ranging from regional perfusion and metabolism to the distribution of binding sites for neuroactive compounds. While none of these new radiopharmaceuticals has yet come into widespread clinical application, the research results already achieved clearly indicate that brain imaging will again be an important aspect of nuclear medicine practice.

Amphetamines↗
PubMed1985

Synthesis of new bis(aminoethanethiol) (BAT) derivatives: possible ligands for 99mTc brain imaging agents.

In developing new brain perfusion imaging agents for single photon emission computed tomography (SPECT), five 99mTc-labeled neutral bis(aminoethanethiol) (BAT) derivatives capable of crossing the blood-brain barrier are reported. The five ligands are prepared by two versatile synthetic methods that can specifically introduce substituents on one of the carbons between two nitrogens. These ligands formed stable and neutral complexes with the reduced 99mTc, using either Sn(II) or sodium borohydride to reduce sodium [99mTc]pertechnetate. The biodistribution in rats was evaluated with [125I]iodoantipyrine, a freely diffusible tracer, as the internal reference. Compounds with a free hydroxyl group, 6 and 15, showed lower brain uptake. High initial brain uptake was observed for compounds 10 and 14, 1.28 and 2.30% dose/organ, respectively. Compounds of this type may be used as a basis for future structural modification to improve brain uptake and retention.

Animals↗
PubMed1985

The effect of anaesthetics on the uptake of brain-imaging agents in rats.

Anaesthetics are shown to affect the brain uptake of two pH-shift brain imaging agents, di-B-(morpholinoethyl)-selenide and N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3-propanediamine significantly. This is probably due to changing regional cerebral blood flow. The present study reaffirms previous observations that small disturbances such as stress and type of anaesthesia will significantly alter the regional cerebral blood flow and, as a consequence, brain uptake in rats. This is an important factor to consider when measuring or comparing brain uptake data.

Anesthetics↗
PubMed1984

Synthesis and biodistribution of neutral lipid-soluble Tc-99m complexes that cross the blood-brain barrier.

Three Tc-99m-labeled neutral 1,2-dithia-5,8-diazacyclodecane (BAT) chelates that are capable of crossing the blood-brain barrier (BBB) were prepared and evaluated. Biodistribution (i.v.) in rats showed a significant brain uptake (1-3%/whole brain) at 2 min. At 15 min the uptake dropped to about a tenth of the original level, indicating free passage in both directions across the BBB. Gamma camera images of a monkey confirmed the high initial brain uptake. This group of Tc-99m BAT compounds clearly exhibited in vivo stability and the ability to cross the BBB after an i.v. injection. Derivatives containing tertiary amine groups should have prolonged brain retention and might be suitable for SPECT studies of brain perfusion.

Animals↗
PubMed1983

A new brain perfusion imaging agent: [I-123]HIPDM:N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-iodobenzyl]-1,3-propanediamine.

Based on the pH-shift mechanism, a new brain imaging agent I-124 HIPDM (N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5-[123I]iodobenzyl]-1,3-propanediamine ) has been developed. This agent can be prepared by a simple exchange reaction suitable for routine clinical use. The physicochemical parameters, partition coefficient vs. pH profile, and protein binding, as well as biodistribution in rats, were very similar to those of I-123 IMP (N-isopropyl-p-iodoamphetamine). High brain uptake was found in animals after i.v. injection. The brain radioactivity persists for at least 1 hr in rats and monkeys. Regional distribution in sections of rat brain appeared to reflect regional perfusion. In conjunction with single-photon emission tomography (SPECT), this agent may provide useful information on local cerebral perfusion in humans.

Amphetamines↗
PubMed1982

Synthesis and tissue distribution study of iodine-labeled benzyl- and xylylamines.

Four iodine-125 labeled mono- and diamines were prepared and evaluated as potential brain-imaging agents. The diamines are analogues of the previously reported selenium-75 labeled diamines, which show high brain uptake and retention. All of the radioiodinated amines display high initial brain uptake in rats after intravenous injection (1.7-2.4% dose/organ). The xylylenediamines show prolonged brain retention (t1/2 approximately 18 h), which is desirable for brain imaging. In contrast, the benzylamine is rapidly cleared from brain tissue (t1/2 approximately 15 min).

Amines↗
PubMed1981

Assessment and interpretation of radiopharmaceutical joint imaging in an animal model of arthritis.

An animal model of arthritis in the rabbit was employed to assess the radioactivity contribution of joint tissues to externally monitored scintigram positivity. Bone contained the greatest total amount of radioactivity whether the imaging agent was technetium pertechnetate or pyrophosphate, although the greatest percent increase in the arthritis joints over control joints was seen in synovium. Mid-shaft bone in the same region as the arthritic joint also showed increased radioactivity compared with control.

Animals↗
PubMed1981

Experimental anti-alveolar basement membrane antibody-mediated pneumonitis. I. The role of increased permeability of the alveolar capillary wall induced by oxygen.

Attempts to produce in animals lung lesions mediated by anti-alveolar basement membrane (ABM) antibodies have thus far been inconclusive. The aim of the present study was to test the hypothesis that increased permeability of the endothelial cell lining is needed before circulating antibodies can gain access and bind to ABM. A goat antiserum was prepared against purified rabbit ABM. After i.v. injection of the gamma-globulin fraction into rabbits, goat IgG was detected in glomerular basement membrane but not in ABM. However, 17 of 19 rabbits injected with anti-ABM antibody after exposure for 62 to 66 hr to 100% oxygen had a diffuse linear binding of goat IgG in ABM and died with pulmonary edema and hemorrhagic pneumonitis. By the paired label isotope technique, uptake of anti-ABM antibodies in lung far exceeded that in kidney. Semiquantitative histologic studies indicated that the lesions in the lung of these rabbits were more severe then those found in rabbits exposed to 100% oxygen and injected with normal goat serum gamma-globulin. None of the latter animals died with pulmonary edema; none was found to have binding of goat IgG in the lung. The results indicate that under normal physiologic conditions the endothelium is a barrier that prevents binding of IgG antibodies to ABM. The increased permeability induced by oxygen in the alveolar capillary wall is a nonimmunologic factor allowing the development of a reproducible model of severe anti-ABM antibody-mediated pneumonitis.

Animals↗
PubMed1980

Synthesis of selenium-75 labeled tertiary diamines: new brain imaging agents.

Selenium-75 labeled tertiary diamines, bis[beta-(N,N-dimethylamino )ethyl] selenide (1), bis[beta-(N,N-diisopropylamino)ethyl] selenide (2), bis(beta-piperidinoethyl) selenide (3), and bis(beta-morpholinoethyl) selenide (4), were prepared by reducing [75Se]selenious acid with sodium borohydride and reacting the intermediate with the N,N-disubstituted aminoethyl chlorides. The effect of pH on lipid solubility (1-octanol/buffer distribution coefficient) was measured for each labeled compound. Biodistribution studies in rats showed high brain uptake for the tertiary diamines, especially for 3 and 4 (1.53 and 1.49% dose/organ, respectively, at 30 min after iv injection). The permanently charged bisquaternary amine, bis[beta-(N,N,N-trimethylammonio)ethyl] selenide (5), showed negligible brain uptake (0.06% dose/organ at 30 min).

Animals↗
PubMed1980

Regional intracellular pH shift: a proposed new mechanism for radiopharmaceutical uptake in brain and other tissues.

This paper proposes a new mechanism for radiopharmaceutical uptake, which may be applicable to a variety of clinical studies. Many tissues and organs have low intracellular pH, either normally or as a result of various metabolic disturbances. We have developed a series of compounds that are neutral and lipid-soluble at blood pH. These molecules can diffuse freely into cells. In those regions where intracellular pH is low, they pick up a hydrogen ion and become charged. In this form they are no longer lipid-soluble and are trapped because they cannot diffuse out of the cell. Studies of the brain uptake of two compounds of this type, Se-75 labeled di-beta-(morpholinoethyl)-selenide (MOSE) and di-beta-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.

Animals↗
PubMed1979

Optimization of the gray scale for photoscanners: concise communication.

A gray scale providing easy visual interpretation of black-and-white photoscan transparencies was determined empirically from psychophysical studies conducted on 50 observers. This optimum gray scale provides equal visualization for equal countrate changes over the entire film range.

Densitometry↗