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F Jamar

Publications and source records attributed to F Jamar.

53 records · Page 3Linked to original sources
PubMed1995

Radiometal labeling of recombinant proteins by a genetically engineered minimal chelation site: technetium-99m coordination by single-chain Fv antibody fusion proteins through a C-terminal cysteinyl peptide.

We describe a method to facilitate radioimaging with technetium-99m (99mTc) by genetic incorporation of a 99mTc chelation site in recombinant single-chain Fv (sFv) antibody proteins. This method relies on fusion of the sFv C terminus with a Gly4Cys peptide that specifically coordinates 99mTc. By using analogues of the 26-10 anti-digoxin sFv as our primary model, we find that addition of the chelate peptide, to form 26-10-1 sFv', does not alter the antigen-binding affinity of sFv. We have demonstrated nearly quantitative chelation of 0.5-50 mCi of 99mTc per mg of 26-10-1 sFv' (1 Ci = 37 GBq). These 99mTc-labeled sFv' complexes are highly stable to challenge with saline buffers, plasma, or diethylenetriaminepentaacetic acid. We find that the 99mTc-labeled 741F8-1 sFv', specific for the c-erbB-2 tumor-associated antigen, is effective in imaging human ovarian carcinoma in a scid mouse tumor xenograft model. This fusion chelate methodology should be applicable to diagnostic imaging with 99mTc and radioimmunotherapy with 186Re or 188Re, and its use could extend beyond the sFv' to other engineered antibodies, recombinant proteins, and synthetic peptides.

Amino Acid Sequence↗
PubMed1995

Exercise gated planar myocardial perfusion imaging using technetium-99m sestamibi for the diagnosis of coronary artery disease: an alternative to exercise tomographic imaging.

Single-photon emission tomography (SPET) using technetium-99m labelled myocardial tracers (e.g. 99mTc-sestamibi) has become one of the most popular myocardial imaging methods for the diagnosis of coronary artery disease (CAD). This prospective study was designed to evaluate the diagnostic performance of 99mTc-sestamibi exercise gated planar myocardial imaging by comparison with both visual and quantitative analyses of SPET. The study was conducted in 115 consecutive patients with known or suspected CAD, including 54 patients with a previous myocardial infarction (MI), referred for exercise testing prior to coronary angiography. Multi-gated planar imaging and SPET were performed after bicycle exercise. The end-diastolic (ED) and SPET images were visually scored (SVi). Myocardial uptake was quantitated on SPET slices using maximum count circumferential profiles (SQu) and defect extent was measured by comparison with gender-matched data sets obtained from 27 controls (< 5% likelihood of CAD). CAD was defined as coronary artery stenosis > 50% and/or regional wall motion abnormality. The cut-off criteria for positivity of the three procedures were determined from receiver operating characteristic (ROC) curves derived from the data of patients without previous MI. The area under the ROC curves was similar for ED, SVi and SQu. This was confirmed by the analysis of sensitivity performed using the ROC curve-derived cut-off criteria, in patients with or without previous MI. SVi was more sensitive than ED in identifying the diseased vessel(s) (ED: 41% vs SVi: 80%; P < 0.0005) but ED was more specific in this respect (ED: 79% vs SVi: 61%; P < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Scintigraphic evaluation of the haemopoietic bone marrow using a 99mTc-anti-granulocyte antibody: a validation study with 52Fe.

To specify the validity of bone marrow scanning using a monoclonal anti-granulocyte antibody labelled with 99mTc (BW 250/183) for the functional assessment of haemopoiesis, we compared this method with 52Fe scan in 16 patients with haematological disorders. The examinations were performed using a rectilinear whole-body scanner and the distribution of the two tracers was assessed visually and quantitatively in anatomical bone marrow segments, the spleen and liver. Qualitative comparison showed concordance in the bone marrow distribution of the two tracers in 83% of the segments. Discrepancies were found in six patients with hypoplastic or aplastic marrow. The spleen was visualized in all cases with the 99mTc-Moab, including nine patients without splenic haemopoiesis (i.e. without spleen uptake of 52Fe). The uptake of the two tracers, quantified in bone marrow segments and the spleen, correlated well (P < 0.001), but not in the liver (NS). The correlation between the uptake values for each patient was excellent, except in cases of aplastic bone marrow. In conclusion, bone marrow scanning using a 99mTc labelled anti-granulocyte monoclonal antibody enables functional evaluation of the distribution of haemopoiesis. Limitations include the evaluation of bone marrow aplasia and identification of splenic haemopoiesis, for which 52Fe remains the tracer of choice.

Adolescent↗
PubMed1995

Inflammatory arthritis: imaging of endothelial cell activation with an indium-111-labeled F(ab')2 fragment of anti-E-selectin monoclonal antibody.

PURPOSE: To use imaging performed with an indium-111-labeled F(ab')2 fragment of monoclonal antibody that recognizes E-selectin (1.2B6) to evaluate inflammation. MATERIALS AND METHODS: After the in vivo immunoreactivity of In-111-F(ab')2 was verified, imaging experiments were conducted on pigs with induced arthritis of the right knee. In-111-labeled 1.2B6-F(ab')2, technetium-99m-hexamethylpropyleneamine oxime-labeled polymorphonuclear leukocytes (PMNs), and iodine-125-MOPC 21-labeled F(ab')2 (the control) were administered by means of intravenous injection. Scintigrams were obtained until 20 hours after injection, and tissue sampling was performed. RESULTS: Scintigrams showed uptake of 1.2B6 in the right knee but only faint filling of the joint space with PMNs. The right knee-to-left knee ratios on images obtained 20 hours after injection of the tracers were 10.8 +/- 3.6 for 1.2B6 and 1.1 +/- 0.4 for PMNs (P < .05). CONCLUSION: Endothelial cell immunotargeting with a radiolabeled anti-E-selectin F(ab')2 monoclonal antibody is feasible for use in imaging of inflammation.

Animals↗
PubMed1995

Granulocyte margination in bone marrow: comparison with margination in the spleen and liver.

The kinetics of radiolabelled granulocytes in the reticuloendothelial system were studied in order to evaluate granulocyte margination in bone marrow. A total of 34 patients took part in a two-part study. In the first part, bone marrow uptake of indium-111-labelled granulocytes was retrospectively analysed in early (3-h) and late (24-h) images in 26 patients, 13 with bronchiectasis and 13 with enclosed abdominal abscesses. The ratios between early and late counts from the bone marrow, spleen, liver and inflammatory lesion were used to quantify granulocyte margination in bone marrow, postulating that if the lesion to bone marrow ratio at 24 h exceeds the value at 3 h, then the "excess" bone marrow counts on the early images would represent margination. In the second part, this suggestion was prospectively tested using Rutland-Patlak graphical and deconvolution analysis of dynamic data, acquired in 8 patients undergoing routine scanning with technetium-99m HMPAO-labelled granulocytes. In the first part of the study, it appeared that the bone marrow is a regional site of granulocyte margination, like the spleen, with at least one-half of the 3-h marrow signal arising from marginated granulocytes, compared with about two-thirds from the spleen. In the second part, it was found that the gradient of the Patlak plot, based on spleen and marrow, continuously decreased, consistent with bi-directional movement of cells between these organs and the blood. Granulocyte pooling in the marrow was confirmed with deconvolution analysis, which generated biphasic retention functions for marrow and spleen. These curves were also consistent with two-way granulocyte exchange, and gave mean cell transit times in both organs of about 12 min and probabilities of extraction on each pass of 5-10%. We conclude that granulocytes marginate in bone marrow to an extent similar to that in the spleen.

Abdominal Abscess↗
PubMed1995

Somatostatin receptor imaging with indium-111-pentetreotide in gastroenteropancreatic neuroendocrine tumors: safety, efficacy and impact on patient management.

UNLABELLED: Indium-111-pentetreotide, a radiolabeled somatostatin analog, has been proposed for imaging tumors bearing somatostatin receptors. This study evaluates the safety, efficacy and impact on patient management of this scintigraphic agent in patients with gastroenteropancreatic (GEP) neuroendocrine tumors. METHODS: We studied 47 consecutive patients with a proven or clinically suspected GEP neuroendocrine tumor who were imaged 4 and 24 hr after injection of 111In-pentetreotide. The patients were monitored for adverse reactions and changes in vital signs or clinical chemistry over 24 hr. The scintigraphic findings were compared with results from conventional imaging methods. The patients were followed over a minimal 6-mo period during which further localization procedures were performed to confirm or refute the additional tumor sites found at scintigraphy. RESULTS: No adverse reactions or clinically relevant changes in clinical chemistry were noted after injection of the radiopharmaceutical. The final diagnosis of a GEP neuroendocrine tumor was retained in 38 patients. Somatostatin receptor-positive lesions were found in 33 of these patients, whereas conventional methods were positive in 31 patients. Of the 54 sites seen by conventional procedures, 50 sites were also detected scintigraphically. CONCLUSION: Indium-111-pentetreotide is a safe, sensitive imaging agent in the detection of GEP neuroendocrine tumor sites. Indium-111-pentetreotide also provides information on the somatostatin receptor status of the tumor and may therefore aid in therapeutic decisions.

Female↗
PubMed1995

Evaluation of disease activity in rheumatoid arthritis and other arthritides using 99mtechnetium labeled nonspecific human immunoglobulin.

OBJECTIVE: To determine the usefulness of 99mtechnetium (99mTc) immunoglobulin scintigraphy (99mTc IgG) in rheumatoid arthritis (RA) and in other arthritides. METHODS: Scintigraphic scores were compared with the Ritchie index and biochemical variables of disease activity. RESULTS: In RA, scintigraphic scores were reproducible and seemed to perform better than clinical scores. Moreover, the scores of synovial uptake correlated significantly with systemic variables of inflammation. Other inflammatory arthritides also disclosed uptake of 99mTc IgG but noninflammatory joints did not. CONCLUSION: Although nonspecific for RA, 99mTc IgG scintigraphy is a reliable tool to evaluate the degree and extent of joint inflammation.

Adult↗
PubMed1994

Noninvasive imaging of E-selectin expression by activated endothelium in urate crystal-induced arthritis.

OBJECTIVE: To assess the expression of the cytokine-inducible endothelial leukocyte adhesion molecule E-selectin during the evolution of urate crystal-induced arthritis, using a recently described radiolabeled monoclonal antibody (MAb) imaging technique. METHODS: Monosodium urate (MSU) crystals and saline alone were injected respectively into the right (inflamed) and left (control) knees of 3 young pigs. Four hours later, 111In-labeled 1.2B6 F(ab')2 (anti-E-selectin MAb) and 125I-labeled MOPC 21 F(ab')2 (control MAb) were injected intravenously. Uptake of 1.2B6 in inflamed and control joints was assessed by scintigraphy 7 and 24 hours after intraarticular injection of MSU crystals. Immunohistochemistry studies and radioactivity counting of tissues were performed postmortem to confirm the observations from scintigraphy. RESULTS: MAb 1.2B6 F(ab')2 scintigraphic images of the knees revealed a significantly increased uptake in the right (inflamed) knee at 7 and 24 hours postinjection, particularly over the joint space. These in vivo images were consistent with E-selectin expression in the inflamed tissue detected by immunohistochemistry and with radioactivity counts postmortem. The synovial localization ratio (inflamed:control synovium counts) was 25.4 +/- 9.7 (mean +/- SD) for the anti-E-selectin MAb compared with 2.5 +/- 0.9 for the control MAb (P < 0.05, by paired Student's t-test). CONCLUSION: E-selectin is expressed by synovial endothelium during the evolution of urate crystal-induced arthritis and can be detected noninvasively using a radiolabeled MAb. This E-selectin imaging technique has considerable potential for the noninvasive assessment of endothelial activation in arthritis and other inflammatory rheumatic diseases.

Animals↗
PubMed1994

Evaluation of technetium-99m-L,L-EC in renal transplant recipients: a comparative study with technetium-99m-MAG3 and iodine-125-OIH.

UNLABELLED: The clinical usefulness of kit-formulated 99mTc-L,L-EC, a new renal tubular tracer agent based on a diaminodithiol ligand was evaluated in a large population of renal transplant recipients. METHODS: Fifty patients with transplants were studied. Five patients with renal insufficiency and five normal volunteers were also included to extend the range of renal function values. The labeling efficiency of 99mTc-L,L-EC in routine conditions, i.e., without HPLC purification, and the safety of the tracer were evaluated. RESULTS: The mean radiochemical purity of 99mTc-L,L-EC determined by thin-layer chromatography was 97.4%. No side effects or significant biochemical changes were observed. The clearance of 99mTc-L,L-EC and 125I-OIH ranged from 10.7 to 417.5 and from 27.6 to 602.7 ml/min/1.73 m2, respectively. The clearance of 99mTc-L,L-EC and 99mTc-MAG3 averaged respectively 71% and 52% of that of 125I-OIH. CONCLUSION: The labeling procedure of kit-formulated 99mTc-L,L-EC is easy and efficient. This tracer is safe and suitable for both imaging and quantitative measurement of the renal tubular function. Technetium-99m-L,L-EC represents an excellent alternative to 99mTc-MAG3.

Adult↗
PubMed1993

52Fe for additional marrow ablation before bone marrow transplantation.

The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

Absorption↗
PubMed1993

Lymphocytic gastritis: an unusual cause of hypoproteinaemia.

Lymphocytic gastritis (LG) is a disorder characterized by diffuse infiltration of the gastric epithelium by small lymphocytes. Its cause remains largely unknown, although several arguments favour an immune origin. Hypoproteinaemia induced by leakage of plasma proteins into the gastric lumen is a rare complication of LG. We report here on three cases of LG whose presenting symptom was lower limb oedema secondary to hypoproteinaemia. The diagnosis was based on radiological, endoscopic and histopathological findings. Radionuclide studies allowed confirmation of the loss of proteins in the stomach. Therapy with omeprazole or H2-receptors antagonists proved to be successful. The relationship between LG and varioliform gastritis is reviewed.

Aged↗
PubMed1992

Influence of ureteral status on kidney washout during technetium-99m-DTPA diuresis renography in children.

To assess the influence of the ureter on renal washout during 99mTc-DTPA diuresis renography, ureteral images were reviewed in 42 children (median age: 5 mo) referred for hydronephrosis. Sixty-minute acquisitions were obtained in hydrated patients under bladder drainage. Furosemide was injected at 30 min. An abnormal ureter was defined as an intense and continuous image of greater than 10 min. A washout index was determined on renal (KT1/2) and ureteral (UT1/2) curves. Curve patterns corresponding to normal (type I), obstructive (II) and nonobstructive (III) cases were described. Compared with the x-ray data, diuresis renography was highly sensitive (91%) and specific (98%) for detecting any abnormality. Despite an obstructive KT1/2 (greater than 20 min), no patient with an abnormal ureter underwent therapy at the ureteropelvic junction. After surgery at the lower level, hydronephrosis regressed. Our data indicate that abnormal ureter findings at diuresis renography have to be recognized before planning therapy for children with hydronephrosis.

Adolescent↗
PubMed1991

Evaluation of two 111In-oxinate formulations for labelling of white blood cells.

This study compares the cell labelling characteristics of two 111In-oxinate formulations. The two preparations differ by the solubilizing agent of the chelate and the total amount of oxine. White blood cell suspensions were obtained by standard separation techniques and were labelled with either of these formulations. The labelling efficiency was higher for 111In-oxinate in aqueous solution (compound B) compared to the preparation where an organic solubilizer was added (compound A) (79.2 +/- 7.7 vs 68.6 +/- 17.6%, respectively, P = 0.03). Red blood cells contaminating the cell suspensions incorporated a higher fraction of 111In if the cells were incubated with the aqueous 111In-oxinate preparation (22.6 +/- 4.6 vs 4.8 +/- 4.6%, respectively, P less than 0.0001). The uptake of activity by polymorphonuclear cells was reduced with compound B (46.1 +/- 12.8 vs 63.8 +/- 15.8%, respectively, P = 0.0002) whereas the fraction retained by mononuclear cells and platelets was similar (31.3 +/- 13.9 vs 31.4 +/- 15.0%, respectively). The recovery from the vial was higher for 111In-oxinate in an organic solution (86.6 +/- 1.82 vs 60.3 +/- 14.3%, respectively, P less than 0.0001). Twenty four hours after administration of the labelled cells, the vascular compartment was less frequently visualized if cells were labelled with compound A (8% of the scintigrams vs 62.5% respectively, P less than 0.0001). High quality images were more often recorded after the administration of cells labelled with compound A (60.0% of the images vs 23.5%, respectively, P less than 0.02). The image quality of scintigrams was not related to any of the other cell labelling parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte Count↗
PubMedDate not supplied

Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven year experience in 20 cases including 9 cases of metastatic midgut carcinoid and 5 cases of metastatic gastrinoma.

The authors report their experience with octreotide in 20 patients (median age 57 years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma. Octreotide (200-750 micrograms/day) was administered bid or tid with regular laboratory controls and morphological assessment. There was a striking improvement of symptoms, particularly in the carcinoid group (reduction of flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma + acromegaly (regression of congestive heart failure) and in the patient with non-metastatic VIPoma. The hormonal markers were markedly reduced, particularly gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin-C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1 PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months, respectively. The patient with acromegaly + ZES died after 6 years of treatment at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism and ZES was not improved by a short course of octreotide (hypoglycemia); he died later of recurrent insulinoma. In conclusion, octreotide is a useful drug to control most of the symptoms related to gut endocrine tumours; it may inhibit tumour growth.

Adolescent↗