The importance of endothelium and interstitial fluid in nuclear medicine.
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Capillary Permeability↗
Biomedical subjects
F Jamar
Publications and source records attributed to F Jamar.
Inadequate detection of accessory spleens and splenosis with laparoscopic splenectomy. A shortcoming of the laparoscopic approach in hematologic diseases.
BACKGROUND: The ultimate goal of surgery for hematological disorders is the complete removal of both the spleen and accessory spleens in order to avoid recurrence of the disease. Whereas splenectomy by open surgery provides excellent results, the validity of laparoscopic splenectomy in this regard remains unknown. OBJECTIVE: The purpose of this study was to evaluate the detection of accessory spleens during laparoscopic splenectomy for hematologic diseases. METHODS: We therefore evaluated the pre-, intra-, and postoperative detection of accessory spleens in a consecutive series of 18 patients treated by elective laparoscopic splenectomy for hematological diseases by using computed tomography (CT) and denatured red blood cell scintigraphy (DRBCS). RESULTS: Preoperative CT, DRBCS, and laparoscopic exploration detected 25%, 25%, and 75% of accessory spleens, respectively. At time of laparoscopy, 16 accessory spleens were detected in seven of the 18 patients (41%). In two patients (11%), laparoscopic exploration failed to detect accessory spleens, whereas preoperative CT (one case) and DRBCS (one case) did reveal them. Postoperatively, during a mean follow-up of 28 months (median, 24; range, 12-44 months), nine patients (50%) showed persistence of splenic tissue by DRBCS, and three of them had signs of disease recurrence. CONCLUSIONS: This prospective clinical study suggests that elective laparoscopic surgery for hematological diseases does not allow complete detection of accessory spleens. Moreover, after such a laparoscopic approach, residual splenic tissue is detectable in half of the patients during the follow-up.
Adolescent↗
Uptake of In-111 pentetreotide by pleural plaques.
Somatostatin receptor imaging with In-111 pentetreotide has been validated for the diagnosis and staging of chest tumors with neuroendocrine differentiation such as bronchial carcinoid and small cell lung cancer. In-111 pentetreotide uptake is not specific for neuroendocrine tumors because somatostatin receptors are also expressed by white blood cells, leading to the in vivo visualization sites of infection sites or active inflammation. Pleural plaques may be due to asbestos exposure or tuberculosis. Presented here are three cases of In-111 pentetreotide uptake in pleural plaques. This uptake by benign lesions may be misleading in the diagnostic work-up of patients with lung tumors.
Aged↗
Can dual-headed 18F-FDG SPET imaging reliably supersede PET in clinical oncology? A comparative study in lung and gastrointestinal tract cancer.
In this study, we prospectively compared the sensitivity of PET and planar SPET (collimated gamma camera) 18F-FDG imaging in patients with lung and gastrointestinal tract cancer and analysed their respective impact on patient management. Twenty-eight patients with lung cancer and 14 with gastro-intestinal tract tumours were scanned on the same day with a PET and a collimated planar SPET gamma camera. The planar SPET procedure consisted of whole-body planar views and a tomographic acquisition centred over the torso or the abdomen, with the total imaging time within the same range as the whole-body PET procedure. The staging of lung cancer patients was accurate in 86% with PET and 64% with planar SPET. Planar SPET would have led to inappropriate therapeutic decisions in 8 of 28 patients, mainly due to undetected distant metastases. In patients with suspected gastrointestinal tract cancer, planar SPET identified 7 of 15 (47%) proven tumour sites, whereas PET identified 14 of 15 (93%). Our results suggest that collimated planar SPET cameras are not a substitute for dedicated PET scanners. The sensitivity for the detection of tumours is unacceptably low and can impair patient management. The use of multiple tomographic acquisitions could improve the sensitivity but would require a longer scanning time.
Colorectal Neoplasms↗
Iodine-131-MIBG scintigraphy in adults: interpretation revisited?
UNLABELLED: Iodine-131-metaiodobenzylguanidine (MIBG) scintigraphy is a reliable method used to diagnose pheochromocytoma. Although the adrenal medulla usually is not visualized, faint uptake can be observed in 16% of the patients 48-72 hr after injection of 18.5-37 MBq 131I-MIBG. We recently observed an increase in the frequency of visualization of the adrenal medulla in patients injected with 74 MBq 131I-MIBG. Therefore, we retrospectively evaluated the pattern of uptake and potential changes between 1984 and 1994. METHODS: Scintigraphic data from 103 patients referred for suspected pheochromocytoma were reviewed randomly. Data from 19 patients with medullary thyroid carcinoma were analyzed separately. Patients were injected with 74 MBq 131I-MIBG and imaged at 24 hr postinjection, 48 hr postinjection, or both. Adrenal uptake was scored visually as 0 (no visible uptake) and 1 (uptake just visible) to 4 (most intense activity in the picture). Semiquantitative indicies were evaluated for discriminating between normal adrenal medullae and pheochromocytomas. Twenty-seven pheochromocytomas were surgically proven in 25 patients. RESULTS: A visual score > or =3 was noted in 81% and 90% of the pheochromocytomas at 24 hr and 48 hr postinjection, respectively. From 1984 to 1988, 16% and 31% of adrenal medullae were seen at 24 and 48 hr postinjection, respectively, whereas from 1989 to 1994, 56% and 73% were visualized at 24 and 48 hr postinjection, respectively. Before 1989, the best cutoff criterion to identify a pheochromocytoma, determined from receiver operating characteristic curve analysis, was a score > or =1 at 24 hr and > or =3 at 48 hr postinjection, with a sensitivity and specificity of 92% and 84% at 24 hr and 92% and 99% at 48 hr postinjection. From 1989, the best cutoff was a score > or =3 at both imaging sessions, with a sensitivity and specificity of 82% and 100% at 24 hr and 100% and 97% at 48 hr postinjection. Among the semiquantitative indicies, the adrenal-to-liver and adrenal-to-heart ratios were the best discriminators between normal and pathological adrenals. They were, however, of little use because of the overlap between normal adrenal medullae and pheochromocytomas. CONCLUSION: The high rate of visualization of the normal adrenal medulla in this study was related to the larger-than-usual injected dose (74 MBq). Over recent years, however, this rate has been increasing, possibly because of the increased specific activity of 31I-MIBG. Adequate interpretation should take into account that a faint or definite uptake may be visible in more than 50% of normal adrenal medullae.
3-Iodobenzylguanidine↗
Endothelial activation in monosodium urate monohydrate crystal-induced inflammation: in vitro and in vivo studies on the roles of tumor necrosis factor alpha and interleukin-1.
OBJECTIVE: There is relatively little direct evidence for the roles of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) in activating endothelium in vivo. The aim of this study was to use in vitro and in vivo models to investigate the contribution of these cytokines to both E-selectin expression and the recruitment of polymorphonuclear cells (PMN) in monosodium urate monohydrate (MSU) crystal-induced inflammation. METHODS: MSU crystals were incubated with freshly isolated mononuclear cells, after which the harvested supernatants were tested for their ability to induce E-selectin expression during coculture with human umbilical vein endothelial cells. Subsequent experiments were performed with the addition of neutralizing anticytokine antibodies/antisera. The role of TNF alpha was then studied in an MSU crystal-induced monarthritis model, in the presence or absence of anti-TNF alpha (5 mg/kg intravenously). 99mtechnetium (99mTc)-labeled PMN cells and (111)indium (111In)-labeled anti-E-selectin monoclonal antibody (MAb) 1.2B6 were intravenously administered 4 hours after intraarticular injection to quantify PMN recruitment and E-selectin expression in inflamed joints. RESULTS: MSU crystals were a potent stimulus for IL-1 and TNF alpha production by monocytes in vitro, and these cytokines fully accounted for MSU crystal-stimulated, monocyte-mediated endothelial activation. In the MSU crystal-induced monarthritis model, TNF alpha blockade was very effective in suppressing both E-selectin expression and PMN emigration into the inflamed joints, as judged by gamma-camera image analysis and postmortem tissue counting following the intravenous injection of 99mTc-PMN and 111In-anti-E-selectin MAb. CONCLUSION: IL-1 and TNF alpha appear to be the only factors released by monocytes following incubation with MSU crystals, which induce E-selectin expression in vitro. Anti-TNF alpha is effective in suppressing endothelial activation and PMN recruitment in vivo E-selectin imaging can be used to assess the endothelial response to therapy and may prove useful for clinical studies.
Animals↗
Living unrelated kidney transplantation.
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Actuarial Analysis↗
Additional myeloablation with 52Fe before bone marrow transplantation.
For many hematological malignancies, high-dose chemoradiotherapy followed by bone marrow transplantation offers the best and sometimes the only chance for cure. However, the main causes of failure of this therapy are relapse and toxicity. In order to selectively deliver higher doses of radiotherapy to the bone marrow and to spare normal organs, we explored 52Fe therapy before a conventional BMT conditioning regimen. Twenty-four patients at high risk for relapse after BMT were included in a phase II study. The median follow-up was 42 months. The median 52Fe dose was 59 mCi. This resulted in a median radiation-absorbed dose (RAD) to the BM of 626 rad. The median RAD to the liver was 338 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 3-year DFS probability was 49% (95% CI: 20-78%). Eight patients have relapsed, three of them in extramedullary sites. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before bone marrow transplantation without excessive toxicity.
Adolescent↗
A comparison between 111In-anti-E-selectin mAb and 99Tcm-labelled human non-specific immunoglobulin in radionuclide imaging of rheumatoid arthritis.
We have developed and validated a method for imaging inflammation using a monoclonal antibody (1.2B6) against E-selectin, an endothelial-cell specific adhesion molecule. This study was undertaken to compare 111In-1.2B6 with 99Tcm-labelled non-specific IgG (99Tcm-HIG) in the detection of synovitis in 11 patients with rheumatoid arthritis (RA). Imaging was performed 4 h and 20-24 h post-injection (pi) of 555 MBq 99Tcm-HIG and 15 MBq 111In-1.2B6. Scintigraphic results were compared with clinical scores of joint involvement. Joint uptake was semiquantitated. The scintigraphic appearances with both tracers correlated well, although 111In-1.2B6 at 24 h showed the highest detection rate. Taking joint tenderness or swelling as evidence of clinical activity, the sensitivity of 111In-1.2B6 at 4 h and 24 h was 69% and 82%, respectively, compared with 69% and 62% for 99Tcm-HIG. 111In-1.2B6 also displayed abnormal activity over a number of joints that appeared silent on clinical examination. Joint-to-soft tissue ratios were higher for 111In-1.2B6 at 24 h (4.0 +/- 1.9; p < 0.0001 vs all) than at 4 h (2.4 +/- 1.4) or than for 99Tcm-HIG at 4 h and 24 h (1.6 +/- 0.5 and 2.3 +/- 0.7, respectively). Net 111In counts over joints increased significantly between 4 h and 24 h (mean change: 54 +/- 40%). This study demonstrates that 111In-1.2B6 scintigraphy is a sensitive method by which to assess RA activity and that targeting is more intense and specific than using 99Tcm-HIG. However, the optimum time for 111In-1.2B6 scintigraphy is 24 h whereas good results are already obtained with 99Tc-HIG at 4 h pi. Current efforts are directed at developing 99Tcm-labelled 1.2B6 for imaging endothelial activation.
Aged↗
99mTc-labelled immunoglobulin scintigraphy in arthritis: an analysis of synovial fluid activity.
The distribution of 99mTc-labelled human polyclonal non-specific immunoglobulin G (HIG) in the synovial fluid was studied in 14 patients with rheumatoid and non-rheumatoid arthritides. Analysis included the determination of the total activity per ml synovial fluid 6 h post-injection (p.i.) of the tracer as well as of the protein- and cell-bound fractions. At 6 h p.i., > 60% of the injected dose remained in plasma as protein-bound radioactivity. Values in the synovial fluid ranged between 0.001 and 0.009% of the injected dose per ml. Importantly, the synovial fluid to plasma ratio was consistently < 1 (range: 0.09-0.43), which is in the range of ratios observed for endogenous proteins in vivo. Similar values were obtained in samples of synovial tissue obtained at surgery in two patients. These data are consistent with the hypothesis that labelled HIG accumulates in the extracellular fluid (both within the synovial tissue and fluid) by non-specific mechanisms (such as increased blood pool and capillary permeability) and does not equilibrate with circulating plasma proteins in accordance with basic knowledge of synovial physiology. In addition, it was found that most of the activity remained bound to the proteins in the fluid and that cell-binding occurred to a very low degree that cannot be considered an important mechanism of uptake of this radiolabelled agent in vivo. These results provide the first evidence in an in vivo human setting that radiolabelled HIG accumulates mainly by non-specific mechanisms in inflamed joints.
Arthritis, Rheumatoid↗
Use of a radiolabeled monoclonal antibody against E-selectin for imaging of endothelial activation in rheumatoid arthritis.
OBJECTIVE: To determine the potential of 111In-labeled anti-E-selectin monoclonal antibody (MAb) to image localized endothelial activation in rheumatoid arthritis (RA). METHODS: Fourteen patients with RA were studied after intravenous administration of 111In-labeled F(ab')2 fragments of MAb against the cytokine-inducible endothelial cell activation antigen E-selectin (MAb 1.2B6). To compare uptake of 1.2B6 with that of nonspecific immunoglobulin, 111In-labeled polyclonal human immunoglobulin (HIG) was separately administered to 6 of these patients and the relative uptake of each tracer was determined. RESULTS: Prominent and discrete uptake of the radiolabeled MAb 1.2B6 was clearly visible in inflamed joints of all patients. Compared with 111In-HIG, 111In-1.2B6 provided superior images in terms of sensitivity and image intensity. Furthermore, the distribution of uptake in inflamed joints was different for the 2 tracers, with 1.2B6 showing a more focal localization in synovium. CONCLUSION: This study demonstrates that it is possible to objectively assess E-selectin expression on activated endothelium in vivo in patients with RA, using a radiolabeled MAb. This technique has considerable potential for monitoring disease activity and response to therapy in inflammatory diseases.
Aged↗
Increased uptake of indium-111 pentetreotide up to 10 years after external thoracic irradiation: report of two cases.
Indium-111 pentetreotide scintigraphy was performed in two patients for the localization of recurrent medullary thyroid carcinoma treated by surgery and external radiotherapy 1 and 10 years earlier. A marked uptake of the radiopharmaceutical was demonstrated in the lung areas that had been irradiated. These cases strongly suggest that this uptake is related to pulmonary fibrosis, a well-known complication of radiotherapy, even long after the irradiation. Therefore, attention must be paid to the avoidance of false-positive interpretation of somatostatin receptor scintigraphy in patients previously treated by radiotherapy.
Aged↗
Technetium-99m L,L-ethylenedicysteine clearance and correlation with iodine-125 orthoiodohippurate for the determination of effective renal plasma flow.
Technetium-99m L,L-ethylenedicysteine (99mTc-L,L-EC) is a new renal tubular tracer that allows the determination of the effective renal plasma flow (ERPF). The aim of this study was to derive simplified methods for the estimation of 99mTc-L,L-EC clearance using one or two plasma samples after bolus injection. Fifty-nine multiple plasma dual-tracer samples (nine samples from 5 to 120 min after injection) were obtained after injection of kit-formulated 99mTc-L,L-EC and iodine-125 orthoiodohippurate (OIH). The studies were performed in 25 stable and 24 unstable transplant recipients, in five patients with renal insufficiency (four on chronic haemodialysis) and in five normal volunteers. This allowed a wide range of renal function values to be covered, with ERPF (estimated by OIH clearance) ranging from 25.4 to 604.0 ml/min. The reference 99mTc-L,L-EC clearance, as calculated from the multisample model, could be estimated from two samples at 15 and 90 min with an error of 11.3 ml/min and from one sample at 90 min with an error of 17.8 ml/min. Using appropriate linear regression analysis, ERPF could be estimated by the two- and one-sample 99mTc-L,L-EC clearance with an error of 24.2 and 22.8 ml/min, respectively. In conclusion, 99mTc-L,L-EC clearance can be accurately estimated by simplified one- or two-sample methods. Moreover, these methods can be used to estimate ERPF with an error that remains acceptable for clinical purposes.
Cysteine↗
Somatostatin receptor imaging in cholangiocarcinoma.
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Bile Duct Neoplasms↗
Characterization of E-selectin expression, leucocyte traffic and clinical sequelae in urate crystal-induced inflammation: an insight into gout.
The self-limiting response to urate crystals allows the exploration of events involved in both the onset and resolution of gout. Using i.v. injected radiolabelled anti-E-selectin monoclonal antibody 1.2b6 together with differentially radiolabelled neutrophils, mononuclear cells and albumin, we have characterized the expression of E-selectin in relation to leucocyte traffic, microvascular permeability and clinical sequelae following intracutaneous injection of monosodium urate crystals. We found that the inflammatory response in this model involved several distinct phases. First, E-selectin expression increased over 2-6 h in the context of increases in neutrophil and mononuclear cell accumulation, and albumin leakage. Secondly, leucocyte accumulation rapidly declined despite persisting E-selectin expression. Thirdly, E-selectin expression peaked at approximately 8 h and then fell despite an increase in clinically detectable erythema and induration. Lastly, these clinical manifestations of inflammation resolved despite the continued presence of urate crystals in the tissues. The further dissection of mechanisms regulating these phases will lead to a better understanding of events in both the pathogenesis and resolution of gout. Of broader significance, this inflammatory model may yield information about the protective events that underly resolution of inflammation, and provide insights into factors which determine chronicity.
Albumins↗
Indium-111-pentetreotide uptake in endocrine tumors and lymphoma.
UNLABELLED: The biodistribution of 111In-pentetreotide was assessed in patients with gastroenteropancreatic (GEP) neuroendocrine tumors or lymphoma and in control patients and analyzed as a function of scanning time, presence or absence of tumor uptake, tumor type and previous octreotide treatment. METHODS: Patients underwent imaging 4 and 24 hr after injection of approximately 200 MBq 111In-pentetreotide. The frequency of organ visualization was assessed on planar views. Total organ and tumor uptake (% injected dose [ID]) was determined using the geometric mean method and regional tissue uptake (% ID/100 ml) by semiquantitative SPECT. RESULTS: Liver, spleen, kidneys and urinary bladder were visualized in all patients. Thyroid, bowel and pituitary were more often visualized at 24 hr than at 4 hr. Activity in the gallbladder, breast, ureters and ascites was only occasionally observed. Total liver, spleen and thyroid uptake was stable over time, whereas kidney activity decreased slightly. At 24 hr, regional uptake was threefold lower in the liver than in the spleen or kidneys and was similar in the three groups. In patients with long-term octreotide therapy, a positive correlation was found between the duration of octreotide therapy and liver or spleen uptake. Total and regional tumor uptake showed high intraindividual and interindividual variations. Total tumor activity was stable over 24 hr in patients with GEP and decreased in those with lymphoma. The mean regional tumor uptake was 10-fold lower in patients with lymphoma than in those with GEP. Cold octreotide injected 24 hr after tracer administration did not result in any displacement of organ and tumor activity. CONCLUSION: Organ uptake seems not to be influenced by the presence of 111In-pentetreotide-positive lesions or by tumor type. Tumor uptake is highly variable among patients and clearly lower in patients with lymphoma than in those with GEP. The widespread of uptake values in tumors indicates that radiotherapy using radiolabeled somatostatin analogs may not be applicable to all patients with 111In-pentetreotide-positive tumors.
Antineoplastic Agents, Hormonal↗
Single-chain Fv radioimmunotargeting.
The availability of engineered antibody species has catalyzed new developments in radioimmunotargeting. This chapter summarized recent studies of single-chain Fv (sFv) proteins, which are minimal antibody binding sites engineered as single polypeptide chains. The single-chain Fv can be as small as 26 kDa monomers or may be engineered as larger fusion proteins designed to self-associate into dimeric or multimeric species. They typically exhibit rapid clearance that results in high targeting specificity within a matter of hours. We have compared different modes of administration to allow further manipulation of their biodistribution and targeting properties. Results of the present study comparing intravenous (i.v.) and intraperitoneal (i.p.) administration show comparable long-term retention in circulation, but the i.v. route showed an initially high peak blood level while i.p. injection did not. As with a single sFv dose, repeated bolus injections of sFv attained high target-to-background ratios, whereas continuous sFv infusion reached a steady state level of free sFv in blood and kidney that exceeded that in tumor xenografts. We observed improved localization of radioiodinated sFv in tumor xenografts if the radioiodine label resisted dehalogenation from the protein, which was accomplished, for example, through conjugation of a para-131I-benzoyl group to Iysyl epsilon-amino groups of the protein. Modification of the sFv by genetic incorporation of a cysteinyl peptide (to form sFv') provided a chelation site for radiometals that simplified incorporation of 99mTc with the opportunity for improved diagnostic imaging in cancer and other diseases. Therapeutic applications of sFv radioimmunotargeting could rely on sFv' complexed to 186Re or 188Re. Engineering sFv of sFv' with increased antigen-binding affinity and appropriately manipulating their mode of administration should promote sustained tumor retention conducive to clinically useful therapeutic indices.
Animals↗
Clearance pathways of soluble immune complexes in the pig. Insights into the adaptive nature of antigen clearance in humans.
Efficient delivery of immune complexes (ICs) to the mononuclear phagocytic system, and subsequent IC processing, may prevent their potentially harmful effects in other tissues and may also be important in the development of humoral immune responses. In mice, rabbits, and primates, the liver and spleen are the main sites of IC clearance. It has been demonstrated previously that the pulmonary capillaries in the pig are lined with macrophages and that certain particulates, including bacteria, localize to this organ. In this study, we used gamma scintigraphy to explore the sites and kinetics of clearance of soluble IC comprising 123I-labeled hepatitis B surface Ag (HBsAg):porcine anti-HBsAg in the Large White pig. At t = 10 min after i.v. injection, 43 +/- 5% (mean +/- SE) IC localized in the lungs, and 36 +/- 6% counts in the liver. At t = 85 min, values were: lungs, 15 +/- 4% and liver, 29 +/- 2%. Findings were similar following intraarterial injection. Complement depletion resulted in more rapid initial IC clearance (t1/2 = 5 min), reduced lung uptake (23 +/- 3% at 10 min), and impaired IC catabolism. In normal animals, 5 to 7% injected IC bound to PBMCs, but no E binding was seen. A fall in PBMC numbers (46 to 59% of baseline), was observed following IC injection. These findings contrast with our previous observations using analogous IC in humans, in which we did not observe any change in peripheral blood leukocyte counts consequent upon complex processing, suggesting that in humans, Es may function as a buffering system for complement-bearing IC in the circulation, preventing their interaction with leukocytes bearing complement and FcR, and the potential activation of these cells.
Animals↗