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.

Scintigraphy with In-111-labeled red cells in intermittent gastrointestinal bleeding.

The site of active intermittent gastrointestinal (GI) bleeding could not be found in a patient until abdominal scintigrams with indium-111-labeled red cells suggested that the bleeding was in the ascending colon. Right hemicolectomy abolished the hemorrhages. The binding of In-111 to the red cell is such that vascular activity could be clearly seen over a 5-day period. Indium-111-labeled red cells might provide an excellent tracer to locate intermittent active GI bleeding.

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.

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.

Accumulation of polymorphonuclear leukocytes in reperfused ischemic canine myocardium: relation with tissue viability assessed by fluorine-18-2-deoxyglucose uptake.

Polymorphonuclear leukocytes may participate in reperfusion injury. Whether leukocytes affect viable or only irreversibly injured tissue is not known. Therefore, we assessed the accumulation of 111In-labeled leukocytes in tissue samples characterized as either ischemic but viable or necrotic by metabolic, histochemical, and ultrastructural criteria. Six open-chest dogs received left anterior descending coronary occlusion for 2 hr followed by 4 hr reperfusion. Myocardial blood flow was determined by microspheres and autologous 111In-labeled leukocytes were injected intravenously. Fluorine-18-2-deoxyglucose, a tracer of exogenous glucose utilization, was injected 3 hr after reperfusion. The dogs were killed 4 hr after reperfusion. The risk and the necrotic regions were assessed following in vivo dye injection and postmortem tetrazolium staining. Myocardial samples were obtained in the ischemic but viable, necrotic and normal zones, and counted for 111In and 18F activity. Compared to normal, leukocytes were entrapped in necrotic regions (111In activity: 207 +/- 73%) where glucose uptake was decreased (26 +/- 15%). A persistent glucose uptake, marker of viability, was mainly seen in risk region (135 +/- 85%) where leukocytes accumulation was moderate in comparison to normal zone (146 +/- 44%). Thus, the glucose uptake observed in viable tissue is mainly related to myocytes metabolism and not to leukocytes metabolism.

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.

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.

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)

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.

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.

Indium-111 leucocyte scanning in the evaluation of painful hip arthroplasty.

Thirty patients with a painful hip arthroplasty had an In-111 leucocyte scan before surgical reexploration. In 12 patients, the In-111 leucocyte scan was abnormal and in all of them, microorganisms were found at the culture of the material from their hips at the operation. Among the 18 patients with a normal scan no infection was found in 17. In one patient, a thick-walled abscess growing Escherichia coli was found. We conclude that In-111 scanning is sensitive, specific and therefore useful in the differential diagnosis of pain after hip arthroplasty.

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.

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.

The spleen and haemolysis: evaluation of the intrasplenic transit time.

The mean intrasplenic red cell transit time (STT) and the slow mixing splenic red cell volume (SSV) have been measured in patients with hereditary spherocytosis (HS), autoimmune haemolytic anaemia (AIHA) and lymphoproliferative disease (LD). There was an inverse relationship between the mean red cell life span (MRCLS) and the STT in HS (r = -0.96, P less than 0.001) and in AIHA (r = -0.90, P less than 0.001). No such relationship existed in LD. The size of the spleen and the SSV were not related to the severity of haemolysis. Our data offer strong evidence for the conditioning effect of the spleen on HS- and AIHA red cells and suggest that the STT is an index of the adverse effect of the spleen on red cells in patients with HS or AIHA.

Diagnosis of heterotopic bone marrow in the mediastinum using 52Fe and positron emission tomography.

A patient with hereditary spherocytosis was admitted with mediastinal masses on the chest X-ray. 52Fe and positron emission tomography (PET) showed uptake of 52Fe in the masses and established the diagnosis of thoracic extramedullary hematopoiesis.

Quantitative assessment of erythropoiesis in bone marrow expansion areas using 52Fe.

Quantitative 52Fe scans were performed in 180 patients. Expansion of bone marrow was observed in 70. This bone marrow expansion was a nearly constant feature in haemolytic anaemia and in sideroblastic anaemia. It occurred in a third of the patients with myelofibrosis. In patients with polycythaemia rubra vera, expansion was noticed in only two out of seven. Erythropoiesis in expansion areas occurred despite persistence of fat in the iliac crest bone marrow biopsy. It could exist with a slight increase in erythropoiesis and might develop only after a long period of erythropoietic stimulation. Increased marrow activity can take place without erythropoietic expansion in long bones. The fraction of iron uptake in expansion areas did not exceed a third of total marrow iron uptake. With increasing erythropoiesis, the increase in iron uptake in expansion areas was less marked than the increase in the central areas. Erythropoiesis in expansion areas was usually not of major quantitative importance but could nevertheless reach the erythropoiesis of a normal adult.