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Biomedical subjects

R E Weiner

Publications and source records attributed to R E Weiner.

At least 19 recordsLinked to original sources
PubMed1999

Imaging infection/inflammations. Pathophysiologic basis and radiopharmaceuticals.

Inflammation is a localized reaction in the microcirculation that is characterized by fluid and leukocyte transport from the blood into the extracellular tissues. The increase in blood flow and loss of endothelial integrity at the site are particularly important in radiopharmaceutical delivery. This alteration of the microvasculature is probably the earliest response to tissue injury. Within hours of inflammation initiation, the site is invaded with large numbers of polymorphonuclear leukocytes (PMN). These cells are led to the site by various chemo-attractants and are able to concentrate in the blood vessels near the inflammation. Upregulation of three families of adhesion molecules, such as the integrins, immunoglobulin supergene and selectins on both the PMN and endothelial cells is an essential component of this process. While both 111In and 99mTc labeled WBC have had undisputed success in detecting infections and inflammations but there are significant limitations. Because of these limitations there have been many attempts to develop new agents which have primarily targeted PMN. The radioactive agent can either bind to the PMN present at the site or be carried to the site bound to PMN. These targets can be PMN-associated antigens or receptors on an activated PMN. Four monoclonal antibodies, CEA-47, BW 250/183, IMMU-NN3 and MCA-480 have been examined extensively for abscess/infection detection in humans.

Humans↗
PubMed1999

The difficult breast.

Mammography is used to screen the population for breast cancer but often is inconclusive. There are several developing techniques to further assess the breast before biopsy that may decrease the number of benign biopsies. These include ultrasound, nuclear medicine, and MR imaging. When a biopsy is deemed necessary, there are several methods used to obtain tissue that are less invasive and less costly than open biopsy. This evolving area of breast evaluation is now filled with great expectation and uncertain future.

Biopsy↗
PubMed1998

Early detection of bleomycin-induced lung injury in rat using indium-111-labeled antibody directed against intercellular adhesion molecule-1.

UNLABELLED: We have investigated whether an (111)In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 ((111)In*aICAM-1) could detect lung injury early in rats treated with bleomycin. METHODS: Rats received an intravenous injection of either (111)In*aICAM-1 or (111)In-labeled normal mouse IgG ((111)In*nmIgG) and were imaged and killed 24 hr later. Lung injury was induced by an intratracheal injection of bleomycin 4 or 24 hr before the rats were killed. After death, tissue was removed and activity was measured, lungs were cryostat-sectioned to detect the presence of ICAM-1 by immunofluorescence, and the up-regulation of LFA-1alpha was examined on blood polymorphonuclear leukocytes (PMNs) using fluorescence-activated cell-sorter (FACS) analysis. RESULTS: In rats injected with (111)In*aICAM-1, the percent injected dose/organ in lungs both at 4 and 24 hr postbleomycin increased significantly compared to the values in either uninjured rats or rats that received (111)In*nmIgG. At 4 and 24 hr postinjury, the target-to-blood (T/B) ratio was 8/1 and 6/1, respectively. For (111)In*nmIgG, the T/B ratio at 4 hr was 0.5/1 and 0.4/1 at 24 hr. In (111)In*aICAM-1 rats injured at 4 or 24 hr, images could easily be distinguished from uninjured rats. All images of (111)In*nmIgG rats showed only cardiac blood-pool and liver activity with little lung activity. Lung ICAM-1 immunofluorescence intensity increased in the bleomycin-treated samples compared to uninjured lungs. Expression of LFA-1alpha on PMNs increased 19% and 210% at 4 hr and 24 hr postinjury, respectively, compared to control values. CONCLUSION: Biodistribution and imaging data demonstrate that (111)In*aICAM-1 can detect early acute bleomycin-induced lung injury. Immunofluorescence and FACS data suggest that (111)In*ICAM-1 uptake is a specific process. This antibody has potential as an early radionuclide detector of acute inflammations.

Animals↗
PubMed1996

Preferential localization of regional metastases from gastroenteropancreatic endocrine tumors with somatostatin-receptor scintigraphy.

Somatostatin-receptor imaging is an effective method for localizing and staging neuroendocrine tumors. We describe patients with gastroenteropancreatic endocrine tumors who underwent preoperative indium In 111 pentetreotide scintigraphy. In 3 patients without prior resections, the results of a 111In pentetreotide scan were positive because of unsuspected regional lymph node metastases without localization of the primary tumors. In these patients, an extensive intraoperative search was required to identify the primary tumors, despite the positive preoperative scan results. In a fourth patient, who had previously undergone resection of a duodenal gastrinoma, 2 regional nodal metastases were identified by a 111In pentetreotide scan.

Adult↗
PubMed1996

Transferrin dependence of Ga (NO3)3 inhibition of growth in human-derived small cell lung cancer cells.

The effect of a combination of anti-transferrin receptor (TFR) antibody, 42/6, and Ga(NO3)3 on cell growth was examined in small cell lung cancer (SCLC) cell lines: classic, NCI-H209, NCI-H345, NCI-H510; and variant, NCI-H82 and NCI-N417. The role of TFR and transferrin (TF) in Ga(NO3)3 cellular uptake was also tested. Exogenous TF did not enhance the cytotoxicity of Ga. At > 3 micrograms/mL, Ga(NO3)3 inhibited growth in all cell lines in TF-supplemented or deficient media. At < 3 micrograms/mL, Ga stimulated growth for all cells but this effect was eliminated by TF or 42/6. Classic SCLC lines required 3-4-fold less exogenous gallium than variant lines to reduce cell number by 50%. The mean Ga uptake (ng/10(6) cells) in H345 and H209 cell lines was 4-5-fold compared to H82 and N417 uptake (P < 0.001). 42/6 reduced exogenous TF-stimulated growth. Antibody plus Ga(NO3)3 caused a slight further cell number decline in all cell lines in TF-supplemented or deficient media. These results suggest that the addition of 42/6 antibody treatment would not increase the effectiveness of Ga(NO3)3 in patients. Both exogenous and endogenous TF and TFR play an important role in Ga uptake in these cells.

Antibodies, Monoclonal↗
PubMed1996

The mechanism of 67Ga localization in malignant disease.

After almost two decades of research, evidence suggests that transferrin receptors are rate-limiting in 67Ga uptake, 67Ga imaging is an in vivo detector of transferring receptors and an indicator of tumor cell proliferation. Moreover, 67Ga can be incorporated into tumor cells by a transferrin receptor-independent process. This pathway could be important in patients with saturated transferrin. Data that appear to support the concept that transferrin receptor-independent transporters are rate-limiting can be resolved by considering the presence of the gallate ion, [67Ga (OH)4]-.

Animals↗
PubMed1996

Biodistribution of indium-111-labeled antibody directed against intercellular adhesion molecule-1.

UNLABELLED: We examined the biodistribution in normal rats of an 111In-labeled mouse monoclonal antibody to rat intercellular adhesion molecule-1 (111In-alCAM-1), as a potential detector of inflammation. METHODS: Indium-111-alCAM-1 or 111In-labeled normal mouse polyclonal immunoglobulin G (111In-nmIgG) was injected into rats. Groups of three to four rats were killed up to 18 hr after injection, and activity was measured in various tissues. Rats were also imaged at 1 and 18 hr after injection. RESULTS: Uptake of 111In-alCAM-1 was greatest in the lung (approximately 10% injected dose [ID]/g at 15 min) and then declined steadily (to approximately 2% ID/g at 18 hr). Lung uptake of 111In-nmIgG was eightfold less than that for 111In-alCAM-1 and did not change throughout the 18 hr. At all time points, blood activity for 111In-alCAM-1 was only 30% to 40% of that for 111In-nmIgG, whereas the percent injected dose per gram was increased more than twofold in the major organs. Compared with 111In-nmIgG, the 111In of alCAM-1 was shifted from the blood and was distributed among the lung kidney, spleen and liver. CONCLUSION: Indium-111-alCAM-1 may be useful as an early inflammation detection agent. Intercellular adhesion molecule-1 upregulation is a very early event in inflammation and rapid removal from the blood of this antibody provides low background in contrast to the usual high background with whole antibodies.

Animals↗
PubMed1994

Quantification of gallium-57 citrate in breast milk.

A woman, 6 months postpartum and nursing her child, had a Ga-67 scintigram. A sample of breast milk obtained at day 2 revealed 2.8% of the injected dose (ID) per liter. The percent ID/L was compared with literature values; the highest concentration was in a report of galactorrhea. Similarity of the gallate ion to phosphate, as a possible explanation for accumulation in the breast, was pointed out. An earlier recommendation that a patient given Ga-67 citrate should discontinue breast feeding for at least 2 weeks was re-examined.

Adult↗
PubMed1992

Loss of radiogallium from lymphoma after initiation of chemotherapy.

A man with a high-grade lymphoma had radiogallium imaging at 48 hours postinjection, revealing three distinct sites of uptake (neck and thorax). Unknown to the authors, the patient was given cytoxan, vincristine, and prednisone intravenously 27 hours after radiogallium administration. The images at 120 hours showed markedly reduced radiogallium activity at all three sites. Possible reasons for the loss of radiogallium from the tumor sites were presented.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Gallium-67 distribution in a man with a decrease in both transferrin and hepatic gallium-67 concentration.

A patient with reduced transferrin concentration had a 67Ga scintigram that showed uptake in a peritoneal abscess, pericarditis and pleural effusion but only faint liver uptake. Gallium-67 activity was measured in liver, lung, muscle and plasma samples obtained at autopsy. The percent injected dose/kg for liver and plasma samples was considerably lower than previously reported while that in muscle and lung tissues values were comparable to prior data. In this patient, sites on transferrin available to bind 67Ga were reduced from the normal 40 microM to 5.2 microM; this in turn increased the concentration of radiogallate from 1% to 7%. This elevated free activity increased 67Ga excretion and reduced the amount of 67Ga*transferrin species. These results and those of previous studies suggest that liver uptake is slower than abscess uptake and more sensitive to concentration of 67Ga*transferrin. Iron status is an important facet of the interpretation of 67Ga scintigrams.

Abscess↗
PubMed1989

Role of phosphate-containing compounds in the transfer of indium-111 and gallium-67 from transferrin to ferritin.

Physiologic concentrations of ATP stimulate the translocation of gallium-67 (67Ga) from human transferrin (TF) to horse ferritin (HoFE). The mechanism of this translocation was examined. One millimolar ATP did not speed the binding of 67Ga or indium-111 (111In) to HoFE. ATP and pyrophosphate (PPi) at 1 mM, did not form high affinity complexes with 67Ga or 111In. ATP and PPi interacted directly with the [67Ga]TF complex and could within minutes increase the amount of nonprotein-bound 67Ga. Serum HCO3- concentration, 30 mM, prevented the ATP-induced dissociation of 67Ga from TF, whereas intracellular concentrations (0.4 and 5 mM) did not. Using a dialysis technique, ATP also stimulated the translocation of 111In from TF to HoFE; however, this process was much slower than with 67Ga. ATP caused an increase in the nonprotein-bound 111In compared to the control. These results suggest the formation of nonprotein-bound nuclide by these phosphate-containing compounds in a kinetically labile form is important to the translocation mechanism.

Adenosine Triphosphate↗
PubMed1988

Scintigraphic and electrophysiological evidence of canine myocardial sympathetic denervation and reinnervation produced by myocardial infarction or phenol application.

Epicardial phenol application or transmural myocardial infarction in dogs produces sympathetic denervation of myocardium apical to the site of the intervention. Because efferent denervation is probably postganglionic, reinnervation most likely occurs but has not been shown. We investigated whether 123I-labeled metaiodobenzylguanidine (MIBG), a norepinephrine analogue taken up by sympathetic nerve terminals, could provide a scintigraphic image that would detect apical sympathetic denervation and possible reinnervation. Dogs underwent MIBG scintigraphic imaging at various times after phenol application or transmural myocardial infarction. The results of MIBG scintigraphy were correlated with electrophysiological responses obtained during ansae subclaviae and norepinephrine stimulation to establish the presence of neural denervation and reinnervation. Apical defects in the MIBG scan, which were associated with either normal perfusion by thallium or a smaller-sized defect, were found consistently in dogs that had apical sympathetic innervation. MIBG scintigraphic images returned to normal after 14 weeks (mean) at a time when reinnervation was shown to have occurred. Thus, the results of MIBG scintigraphy correlated accurately with the presence of denervation and reinnervation established by neuroelectrophysiological testing. Supersensitive refractory period shortening in response to norepinephrine infusion was present after denervation and persisted for more than 3 weeks after scintigraphic and electrophysiological evidence of reinnervation. Conclusions are that 1) MIBG can be used noninvasively to determine the presence of regional myocardial efferent sympathetic denervation and subsequent reinnervation, 2) reinnervation occurs after phenol application or transmural myocardial infarction, and 3) denervation supersensitivity persists even after reinnervation occurs.

3-Iodobenzylguanidine↗
PubMed1987

Influence of various factors on binding of 67Ga to polymorphonuclear leukocytes.

We have studied in vitro, factors that influence the uptake of 67Ga-citrate by human polymorphonuclear leukocytes. Citrate at 20 mM concentration decreased the uptake to 1% of control values. Uptake increased as a function of increased microCi of 67Ga/10(7) cells added and incubation time from 0 to 120 min. Uptake decreased somewhat as the incubation pH was lowered from 7.4 to 6.0. Our results suggest that, in vivo, these cells would accumulate 67Ga as the inflammatory lesion progresses while the acidic milieu would modestly reduce uptake.

Citrates↗
PubMed1985

Compounds which mediate gallium-67 transfer from lactoferrin to ferritin.

The influence of various low molecular weight compounds on the transfer of 67Ga from human lactoferrin (LF) to horse spleen ferritin (HoFE) has been examined in vitro. When LF*67Ga complex was placed in competition with HoFE using a dialysis system the initial transfer rate (TR) of 67Ga to HoFE was slow and continuous. In the presence of 1 mM pyrophosphate (PPi) ascorbate and adenosine triphosphate (ATP), the TR was dramatically enhanced. This effect was concentration sensitive since reduction of the ATP to 0.1 mM eliminated the enhancement. Other intracellular compounds did not significantly influence the TR. Although PPi and ascorbate ions yielded larger TR's, ATP was more effective in the promotion of 67Ga transfer to HoFE. When the LF/HoFE concentration ratio was decreased, in the presence of ATP, the transfer of 67Ga was significantly increased. These results suggest that ferritin present intracellularly could remove and retain 67Ga entering the cell in the form of a LF*67Ga complex. Moreover, increased synthesis of ferritin and cytosolic phosphate compounds would appear to enhance this process.

Adenosine Triphosphate↗