Liposome distribution after intravenous and selective intraarterial infusion in dogs

In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels.     

Diffuse bone marrow involvement of Hodgkin lymphoma mimics hematopoietic cytokine-mediated FDG uptake on FDG PET imaging

Whole-body fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) has been useful in the management of a variety of malignancies. In patients with chemotherapy followed by bone marrow stimulants such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, the bone marrow will have diffuse, increased FDG accumulation. Therefore, diffuse bone marrow FDG uptake is commonly attributable to the effect of hematopoietic cytokines. However, diffuse bone marrow FDG uptake can also be caused by bone marrow involvement by malignancy. The authors report a patient with diffuse bone marrow involvement of Hodgkin disease that appears indistinguishable from hematopoietic cytokine-mediated FDG bone marrow uptake.     

Distribution of radiolabeled multilamellar liposomes injected intralymphatically and subcutaneously

The distribution of negatively charged multilamellar vesicles (MLV) composed of dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol administered subcutaneously (s.c.) and intralymphatically (i.l.) was studied in rats and dogs. In rats, the drainage of 99mTc-MLV from the s.c. space was slow, with 35% of the activity still remaining at the site of injection after 48 h and minimal systemic distribution (less than 5% at any time point). In the dog, 99mTc-MLV and 111In-MLV injected s.c. on the dorsal surface of a hindpaw were drained both by the lymphatic system and the systemic circulation; at 24 and 72 h, significant activity still remained at the site of injection. Lymphatic uptake was almost limited to the popliteal nodes and was enhanced by dividing the dose in several s.c. injections. Liver and kidney uptake was also observed, most likely as a result of direct liposome absorption into the systemic circulation. The i.l. administration (via left hindpaw) of 99mTc-MLV to a dog resulted in an immediate uptake in the abdominal and mediastinal lymph nodes, and in the liver and spleen. Compared with small unilamellar vesicles, MLV injected s.c. can provide a slower and more prolonged delivery of drugs to the regional lymph nodes.     

Chemokine receptor-4 targeted PET/CT with 68 Ga-Pentixafor in assessment of newly diagnosed multiple myeloma: comparison to 18 F-FDG PET/CT

18F-FDG PET/CT has some limitations in the evaluation of multiple myeloma (MM). Since chemokine receptor-4 is overexpressed in MM, we perform a prospective cohort study to compare the performance of 68Ga-Pentixafor and 18F-FDG PET/CT in newly diagnosed MM. Thirty patients with newly diagnosed MM were recruited. All patients underwent 68Ga-Pentixafor and18F-FDG PET/CT within 1 week after enrollment. A positive PET/CT was defined as the presence of focal PET-positive lesions in bone marrow or diffuse bone marrow patterns (uptake > liver). Bone marrow uptake values in 68Ga-Pentixafor and18F-FDG PET/CT (total bone marrow glycolysis [TBmGFDG], total bone marrow uptake with 68Ga-Pentixafor [TBmUCXCR4], total bone marrow volume [TBmV], SUVmean, and SUVmax) were obtained by drawing total bone marrow volume of interest on PET/CT. The positive rates of the PET/CT scans were statistically compared, and the correlation between quantitative bone marrow uptake values and clinical characteristics, laboratory findings, and staging was analyzed. 68Ga-Pentixafor PET/CT had a higher positive rate than 18F-FDG PET/CT in recruited patients (93.3 vs. 53.3%, p = 0.0005). In quantitative analysis, bone marrow uptake values in 68Ga-Pentixafor (TBmUCXCR4, SUVmax, and SUVmean) were positively correlated with end organ damage, staging, and laboratory biomarkers related to tumor burden including serum β2-microglobulin, serum free light chain, and 24-h urine light chain (p < 0.05). In 18F-FDG PET/CT, only the SUVmean of total bone marrow was positively correlated with serum free light chain and 24-h urine light chain (p < 0.05). 68Ga-Pentixafor PET/CT is promising in assessment of newly diagnosed MM. NCT 03436342     

Bone marrow with diffuse tumor infiltration in patients with lymphoproliferative diseases: dynamic gadolinium-enhanced MR imaging

PURPOSE: To evaluate gadolinium enhancement of bone marrow in patients with lymphoproliferative diseases and diffuse bone marrow involvement. MATERIALS AND METHODS: Dynamic contrast material-enhanced magnetic resonance (MR) imaging of the thoracolumbar spine was performed in 42 patients with histologically proved diffuse bone marrow involvement and newly diagnosed myeloma (n = 31), non-Hodgkin lymphoma (n = 8), or Hodgkin disease (n = 3). The maximum percentage of enhancement (Emax), enhancement slope, and enhancement washout were determined from enhancement time curves (ETCs). A three-grade system for scoring bone marrow involvement was based on the percentage of neoplastic cells in bone marrow samples. Quantitative ETC values for the 42 patients were compared with ETC values for healthy subjects and with grades of bone marrow involvement by using mean t test comparisons. Receiver operating characteristic (ROC) analysis was conducted by comparing Emax values between patients with and those without bone marrow involvement. Baseline and follow-up MR imaging findings were compared in nine patients. RESULTS: Significant differences in Emax (P <.001), slope (P <.001), and washout (P =.005) were found between subjects with normal bone marrow and patients with diffuse bone marrow involvement. ROC analysis results showed Emax values to have a diagnostic accuracy of 99%. Emax, slope, and washout values increased with increasing bone marrow involvement grade. The mean Emax increased from 339% to 737%. Contrast enhancement decreased after treatment in all six patients who responded to treatment but not in two of three patients who did not respond to treatment. CONCLUSION: Dynamic contrast-enhanced MR images can demonstrate increased bone marrow enhancement in patients with lymphoproliferative diseases and marrow involvement.     

Can [18F]fluorodeoxyglucose positron emission tomography imaging complement biopsy results from the iliac crest for the detection of bone marrow involvement in patients with malignant lymphoma?

OBJECTIVES: To assess the usefulness of [18F]fluorodeoxyglucose positron emission tomography in the detection of bone marrow involvement in malignant lymphoma, and its impact in clinical management. METHODS: One hundred and six consecutive patients with a confirmed diagnosis of lymphoma, referred for staging or restaging of Hodgkin's lymphoma (n=18) or non-Hodgkin's lymphoma (n=88), were reviewed retrospectively. A positron emission tomography scan and bone marrow biopsy of the iliac crest were performed in all patients. The assessment of bone marrow involvement by lymphoma was confirmed by histology and/or progression of bone marrow lesions in clinical follow-up. RESULTS: In 28 of 106 patients, bone marrow involvement was found. Positron emission tomography was more sensitive (86%) than bone marrow biopsy (57%). Positron emission tomography and bone marrow biopsy were concordant by positive correlation in 12 of 28 cases (43%) and by negative correlation in 77 of 78 cases (99%). Ten cases of non-Hodgkin's lymphoma and two cases of Hodgkin's lymphoma with positive positron emission tomography results and an initial negative bone marrow biopsy showed clinical progression of the bone marrow lesions and/or subsequent positive histology. These were considered as false-negative results for bone marrow biopsy. In seven of the 12 positive cases with negative bone marrow biopsy, positron emission tomography uptake distant from the site of the biopsy was seen. In four cases of follicular lymphoma, the bone marrow biopsy was positive and the positron emission tomography scan was normal. CONCLUSIONS: Positron emission tomography and bone marrow biopsy are complementary in assessing the presence of bone marrow involvement in patients with malignant lymphoma. In our series, positron emission tomography was more sensitive than bone marrow biopsy in Hodgkin's and non-Hodgkin's lymphoma, except in follicular lymphoma.     

Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

Purpose  To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. Methods  From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Results  Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher’s exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Conclusion  Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement.     

淋巴瘤骨髓浸润的18F-FDG PET显像研究

目的 用^18F-脱氧葡萄糖（FDG）PET显像研究淋巴瘤细胞骨髓浸润。方法 恶性淋巴癌患者30例，其中非霍奇金淋巴瘤（NHL）20例、霍奇金病（HD）10例，进行全身^18F-FDG PET显像。局灶性边缘清楚的淋巴结相应区域^18F-FDG浓聚视为恶性淋巴结显影。利用灰度色标，视觉分析骨髓及肝脏内^18F-FDG浓聚情况。骨髓的^18F-FDG分布不均，摄取高于肝脏，判断为骨髓^18F-FDG摄取异常；骨髓的^18F-FDG分布均匀，摄取低于或等于肝脏，判断为骨髓^18F-FDG摄取正常。所有患者均行髂棘的骨髓活组织检查。结果 30例中18例有淋巴结摄取^18F-FDG；12例淋巴结摄取^18F-FDG阴性患者中，8例NHL，4例HD。有26例患者的骨髓^18F-FDG摄取情况与骨髓组织学检查结果一致，其中骨髓有淋巴细胞浸润7例，无淋巴细胞浸润19例。有3例骨髓组织学检查阴性的患者，^18F-FDG PET示骨髓^18F-FDG摄取异常、骨髓有淋巴细胞浸润；1例NHL患者，骨髓组织学检查阳性但^18F-FDG PET示骨髓^18F-FDG摄取正常。结论 ^18F-DG PET全身显像能正确评价骨髓淋巴细胞浸润情况，减少对淋巴瘤分期所进行的骨髓组织学检查。     

Prognostic value of FDG uptake by the bone marrow in squamous cell carcinoma of the head and neck

BACKGROUND: The appearance of natural suppressor cells and circulating endothelial progenitor cells in tumour tissue has been associated with myelopoetic stimulation by growth factors that may increase fluorodeoxyglucose (FDG) uptake by the bone marrow and high FDG uptake by bone marrow in patients suffering from human malignancies is a not uncommon finding. METHODS: This study looked at the relationship between bone marrow FDG uptake, biochemical (Hb level, RBC count, WBC count and platelet count), clinical and radiological findings and outcome in a series of 35 patients suffering from squamous cell carcinoma of the head and neck (SCCHN), consecutively referred for FDG PET as part of their routine staging procedure. RESULTS AND CONCLUSION: In SCCHN, mean FDG standardized uptake values (SUVs) of the primary tumour correlate significantly with blood WBC count (r=0.44; P=0.011, Bonferroni corrected P=0.04) and mean FDG SUVs of bone marrow are significantly correlated to the maximum FDG SUVs of the primary tumour (r=0.523; P=0.002). Finally, FDG uptake by the bone marrow is related to disease-free and overall survival. These findings warrant confirmation in a larger patient series.     

Modulation of water proton relaxation rates by liposomes containing paramagnetic materials

Liposomes containing paramagnetic chemicals have significant potential for enhancing the effectiveness and selectivity of contrast agents in magnetic resonance imaging. We have studied the interactions of water, liposomes, and contrast agents using NMR and ESR. We find that the permeability of liposomes to water is of major importance in determining the effects of these systems on water proton relaxation. Key factors include (1) liposome composition, which determines the phospholipid membrane phase behavior as a function of temperature; (2) liposome structure (unilamellar or multilamellar); (3) location of the contrast agent in the liposome (aqueous space or lipid membrane); and (4) binding of contrast agents by liposomes. By appropriate selection of these factors it is possible to obtain effective proton relaxation enhancement in a manner suitable for particular experimental or clinical needs for contrast in MRI. For maximum relaxivity using lipophilic nitroxides, the optimum system appears to be 5-doxyl stearate in multilamellar vesicles with a membrane composition that gives a phase transition temperature slightly above body temperature.     

Splenic fluorodeoxyglucose uptake increased by granulocyte colony-stimulating factor therapy: PET imaging results.

Using PET, we investigated the change in 18F-fluorordeoxyglucose (FDG) uptake in the spleen after granulocyte colony-stimulating factor (G-CSF) treatment. METHODS: Forty-two FDG PET scans in 12 patients with locally advanced breast cancer who received G-CSF treatment were studied (12 baseline, 10 during G-CSF, 20 after G-CSF treatment). The PET images obtained at 50-60 and 60-70 min after intravenous FDG (370 MBq) injection were assessed visually and were compared with those before G-CSF treatment. For a semiquantitative index of FDG uptake, we determined the standardized uptake value calculated on the basis of predicted lean body mass (SUL) on these images, and we calculated the SUL ratios normalized to their baseline SUL values. RESULTS: During G-CSF treatment (n = 10), 9 scans (90%) showed increased splenic FDG uptake (3 slightly, 6 substantially). After G-CSF treatment (n = 20), 13 (65%) showed no change, 7 (35%) showed slightly increased uptake, but no case showed substantially increased FDG uptake in the spleen (P = 0.0003). Out of 30 PET scans obtained during and after G-CSF treatment, 16 (53%) showed increased FDG uptake in the spleen (10 slightly, 6 substantially), whereas 26 (87%) showed increased bone marrow FDG uptake (14 slightly, 12 substantially). The FDG uptake in other normal organs (liver, blood and lung) showed no change during or after G-CSF treatment. Similar to the change in the bone marrow, the SULs in the spleen significantly increased during G-CSF treatment (baseline, 1.50+/-0.31, versus during G-CSF, 2.69+/-0.84; P = 0.0004), then decreased after discontinuation of G-CSF (1.65+/-0.23). There was a significant correlation between the SUL ratios in the spleen and those in the bone marrow (r = 0.778, P < 0.0001), whereas there were no correlations between those in other organs and those in the bone marrow. CONCLUSION: Substantially increased FDG uptake was observed in the spleen during and after G-CSF treatment, although this change was less frequent and not as marked as the change observed in the bone marrow. The recognition and understanding of this phenomenon will be increasingly important when interpreting FDG PET images in cancer patients to avoid confusing this normal phenomenon with pathological splenic (tumor) involvement.     

Diffuse bone marrow uptake on whole-body F-18 fluorodeoxyglucose positron emission tomography in a patient taking recombinant erythropoietin

F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used extensively in oncology to diagnose, stage, and restage patients with various malignancies. Many patients treated for malignancies develop neutropenia secondary to marrow suppressive chemotherapy and are subsequently treated with synthetic hematopoietic growth factors (HGF), both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte-colony-stimulating factor (G-CSF). Patients taking HGF can present a diagnostic challenge for those interpreting PET because they can demonstrate diffuse marrow uptake on FDG-PET scans, mimicking diffuse bone marrow metastases. It has not been reported whether bone marrow uptake is affected on PET scans in patients taking erythropoietin, the erythroid-specific cell-line stimulator. We report a case of extensive diffuse bone marrow uptake in a 77-year-old man with a history of colon cancer who began taking erythropoietin 3 weeks before his PET scan. This case demonstrates the need to consider erythropoietin in the differential diagnosis of possible etiologies causing diffuse bone marrow uptake on PET scans.     

An analytic dosimetry study for the use of radionuclide-liposome conjugates in internal radiotherapy.

A dosimetric analysis has been performed to evaluate the potential of liposome systems as carriers of radionuclides in internal radiotherapy. METHODS: Pharmacokinetic data for a variety of liposome constructs (multilamellar vesicles [MLV]; small unilamellar vesicles [SUV]; and sterically stabilized liposomes, monosialoganglioside [G(M1)]-coated) were used to obtain tumor and normal-organ absorbed dose estimates for (67)Cu, (188)Re, (90)Y, and (131)I. Dosimetry was performed for two tumor models: subcutaneous Ehrlich ascites tumor, growing intramuscularly, and C26 colon carcinoma, growing intrahepatically. Dose estimates were obtained using the MIRD schema. Tumor doses were obtained assuming local deposition of electron energy; photon contributions were incorporated assuming spheric tumor geometry. With the conservative assumption that intravenously administered liposomes achieve rapid equilibration with the red marrow extracellular fluid volume, red marrow absorbed dose estimates were obtained from blood kinetics. RESULTS: For intramuscular tumors, absorbed dose ratios for tumor to red marrow ranged from 0.93 ((131)I-MLV) to 13.9 ((90)Y-SUV). Tumor-to-liver ratios ranged from 0.08 ((188)Re-MLV) to 0.92 ((188)Re-SUV); corresponding values for tumor to spleen were 0.13 ((90)Y-MLV) and 0.54 ((188)Re-G(M1)). The optimal combination of radionuclide and liposome system was obtained with (90)Y-SUV. Tumor-to-liver ratios for the G(M1)-coated construct were greatest when the tumor was intrahepatic (1.13 for (90)Y). For a given liposome system, absorbed dose ratios for tumor to normal tissue exhibited up to a twofold variation depending on the radionuclide selected. CONCLUSION: This study provides a dosimetric evaluation for the use of some liposome systems as carriers in targeted radionuclide therapy. Although much further work must be undertaken before any clinical application is considered, these results suggest that radionuclide targeting using liposomes is feasible and may have the advantage of reduced red marrow absorbed dose.     

Osteosarcoma: relation between extent of marrow infiltration on CT and frequency of lung metastases

Thirty-seven patients with osteosarcoma were evaluated by CT of both the involved bone and the lungs. The ratio of the extent (E) of the involved marrow segment to the length (L) of involved bone (E/L) was correlated with the presence and subsequent development of pulmonary metastases. The marrow was evaluated by CT for the presence of tumor by measuring mean attenuation coefficients on serial axial scans. Three patient groups were identified: group 1 consisted of seven patients with lung metastases at presentation (mean E/L = 61%), group 2 consisted of 10 patients who developed lung metastases or recurrent tumor either during or after chemotherapy (mean E/L = 39%), and group 3 consisted of 20 patients who completed therapy and remained disease-free (mean E/L = 28%). All patients received chemotherapy in addition to surgical resection except for two patients in group 1. No patient with an E/L ratio greater than 50% remained disease-free for more than 14 months after the initial diagnosis. Fifty percent or greater involvement of the marrow cavity thus carries a particularly poor prognosis, and its absence or presence can be used as a significant prognostic aid in osteosarcoma.     

Severity of bone marrow involvement in patients with Gaucher's disease evaluated by scintigraphy with 99mTc-sestamibi.

Gaucher's disease is a lysosomal storage disorder due to a genetically transmitted deficiency of the enzyme glucocerebrosidase. In the most common form of the disease (type 1), accumulation of glucosylceramide in the reticuloendothelial cells of liver, spleen, and bone marrow leads to visceromegaly, anemia, thrombocytopenia, and osteopenia. Skeletal manifestations secondary to infiltration of the bone marrow by Gaucher's cells are detectable by radiography only in advanced stages. Imaging of bone marrow involvement can be performed indirectly by magnetic resonance techniques or by bone marrow scintigraphy with radiocolloids. However, both procedures lack specificity because the normal bone marrow, rather than the pathologic process, is imaged. The aim of this study was to assess the reliability of (99m)Tc-sestamibi scintigraphy for direct evaluation of bone marrow involvement. METHODS: Seventy-two patients with type 1 and 2 patients with type 3 Gaucher's disease (35 males, 39 females) were enrolled in the study. The mean age +/- SD was 31.9 +/- 16.5 y (range, 3-76 y), and the average duration of the disease manifestations when performing scintigraphy was 12.95 y (median, 10.5 y; range, 0-44 y). Forty-three of 74 patients had never received enzyme replacement therapy (ERT), whereas 31 patients were already being treated with ERT. (99m)Tc-Sestamibi was injected intravenously (6-8 MBq/kg of body weight) and imaging was recorded at the lower limbs 30 min after injection, at the plateau of tracer accumulation in the involved bone marrow. The scans were evaluated visually, assigning a semiquantitative score based on the extension and intensity of uptake in the bone marrow of the lower limbs (0 = no uptake; 8 = maximum uptake). The scintigraphic score was entered into complex statistical analysis, which included a series of clinical and blood chemistry parameters defining overall severity of the disease. RESULTS: (99m)Tc-Sestamibi scintigraphy showed that 71 of 74 patients had some degree of bone marrow involvement. The scintigraphic score was highly correlated with an overall clinical severity score index (SSI) and with various parameters contributing to the SSI, either positively or negatively. The highest correlation of the scintigraphic score was found with an overall biochemical marker of disease severity (serum chitotriosidase). ERT-naive patients showed high correlation of the scintigraphic score with the clinical SSI, with a radiographically based score, and with serum chitotriosidase. In the ERT-treated patients, the scintigraphic score was correlated with the clinical SSI, with hepatomegaly, and with hemoglobin. CONCLUSION: (99m)Tc-Sestamibi uptake reliably identifies bone marrow infiltration by Gaucher's cells. The scintigraphic score is helpful for defining the severity of bone marrow involvement and for comparing patients. (99m)Tc-Sestamibi scintigraphy, which provides topographic information about the sites involved by the disease, is highly correlated with other parameters of disease severity and appears to correlate with response to ERT.     

18F-FLT PET in hematologic disorders: a novel technique to analyze the bone marrow compartment.

Few diagnostic procedures are available to determine the degree of bone marrow cellularity and the numbers of cycling cells in patients with bone marrow disorders. Noninvasive imaging of the bone marrow compartment may be helpful. The PET tracer 3'-fluoro-3'-deoxy-L-thymidine (18F-FLT) has been developed recently. 18F-FLT uptake is related to the rate of DNA synthesis and increases with higher proliferation rates in many types of cancer. Background uptake of 18F-FLT in bone marrow is common. 18F-FLT PET might, therefore, visualize the high cycling activity of hematopoietic cells in the bone marrow compartment. Therefore, we investigated the feasibility of visualization and quantification of the activity of the bone marrow compartment with 18F-FLT PET to distinguish different hematologic disorders. METHODS: Clinical and laboratory data of 18 patients with myelodysplasia (MDS), chronic myeloproliferative disorders, myelofibrosis, aplastic anemia, or multiple myeloma were correlated with the results of 18F-FLT PET using visual analysis and the standardized uptake value (SUV). Findings were compared with those of healthy control subjects (n = 14). RESULTS: With SUV and visual analysis, a distinction could be made between MDS (n = 9), chronic myeloproliferative disorders (n = 3), and myelofibrosis (n = 3) compared with healthy control subjects. A significant increase in 18F-FLT uptake was observed in all of the studied patients with MDS and myeloproliferative disorders. In contrast, patients with myelofibrosis and aplastic anemia (n = 1) demonstrated a decline in bone marrow 18F-FLT uptake compared with healthy control subjects. Comparable results were observed in osteolytic lesions of patients with multiple myeloma (n = 2). CONCLUSION: 18F-FLT PET can be used to visualize the proliferative activity of the bone marrow compartment and may be helpful to distinguish separate hematologic disorders.     

The importance of bone marrow examination for hemoblastoses]

Morphological bone marrow evaluation is an integral component in staging patients with hematological malignancies. In acute leukemias or myelodysplastic syndromes cytologic examination is crucial since it allows precise analysis on the individual cell level. Histological examination of an iliac crest trephine biopsy is mandatory in malignant lymphomas because of the frequent nodular involvement of bone marrow in these diseases. In recent years magnetic resonance tomography (MRT) has been shown to be a sensitive method for detecting marrow infiltration in a variety of marrow diseases. In malignancies with focal marrow involvement, such as malignant lymphoma, MRT is today a useful complement to morphological bone marrow evaluation.     

Prevention of the hemodynamic effects of iopromide-carrying liposomes in rats and pigs

RATIONALE AND OBJECTIVES: Intravenous injection of liposomes is able to trigger allergy-like reactions that affect the cardiopulmonary system. The mechanism of these effects is still not totally clear. Because prediction of adverse reactions and the consequent exclusion of reactive patients do not seem feasible, prevention might have a considerable impact. METHODS: Two small, multilamellar liposome batches with the encapsulated contrast agent iopromide, which differed by size and buffer composition, were injected into anesthetized rats (n = 5 per group) and pigs (n = 6 per group). Blood pressure (BP), cardiac output (CO), contractility (dP/dt; in rats), total peripheral resistance (TPR; in rats), pulmonary vascular resistance (in pigs), and pulmonary arterial pressure (PAP; in pigs) were monitored. Saline, mannitol solution, the two buffers, and the contrast medium were used as controls. RESULTS: Significant changes in hemodynamic parameters were observed not only between liposomes and controls but also between the two liposome preparations. In rats, a significant decrease in BP followed by its normalization and subsequent increase, a decrease in CO followed by an increase, a decrease in TPR, and a decrease in dP/dt followed by an increase were observed. In pigs, the effects were different both in quality and in quantity (more intense) compared with those in rats. In this species, an increase in BP, a decrease in CO, an increase in TPR, and an increase in PAP were found. Pretreatment with acetylsalicylic acid was able to prevent the hemodynamic changes induced by the liposomes. CONCLUSIONS: Allergy-like side effects induced by liposome injection strongly depend on the size, electric charge, and composition of the particles. The mechanism triggered by liposome injection probably is complex and can be effectively blocked by pretreatment with acetylsalicylic acid.     

99mTc-PEG liposomes for the scintigraphic detection of infection and inflammation: clinical evaluation.

Polyethyleneglycol (PEG) liposomes have been shown to be excellent vehicles for scintigraphic imaging of infection and inflammation in various experimental models. In this article we report on a series of patients with possible infectious and inflammatory disease in whom the performance of 99mTc-PEG liposomes was evaluated. The results of 99mTc-PEG liposome scintigraphy were directly compared with those of 111In-immunoglobulin G (IgG) scintigraphy. METHODS: Thirty-five patients (22 men, 13 women; mean age, 51 y; range, 20-76 y), suspected of having infectious or inflammatory disease, received 740 MBq 99mTc-PEG liposomes intravenously. Imaging was performed at 4 and 24 h after injection. Patients received 75 MBq 111In-IgG 24 h after administration of the liposomes. The scintigraphic results were compared and verified by culture, biopsy, surgery, and follow-up of at least 6 mo. RESULTS: Of the 16 proven infections and inflammations, 15 were detected by 99mTc-PEG liposome scintigraphy: soft-tissue infection (n = 3), septic arthritis (n = 3), autoimmune polyarthritis (n = 2), infected hip prosthesis (n = 1), infected osteosynthesis (n = 1), spondylodiscitis (n = 1), infected aortic prosthesis (n = 1), colitis (n = 1), abdominal abscess (n = 1), and pneumonia (n = 1). 99mTc-PEG liposome and 111In-IgG scintigraphy both missed 1 case of endocarditis. In addition, an 111In-IgG scan of a patient with mild soft-tissue infection was false-negative. Concordantly false-positive scans were recorded from 2 patients, both with uninfected pseudarthrosis and focal signs of sterile inflammation. During liposomal administration, 1 patient experienced flushing and chest tightness, which rapidly disappeared after lowering the infusion rate. No other adverse events were observed. CONCLUSION: This clinical evaluation of 99mTc-PEG liposomes shows that focal infection and inflammation can be adequately imaged with this new agent. The performance of 99mTc-PEG liposomes is at least as effective as that of 111In-IgG. With the simple and safe preparation and the physical and logistic advantages of a 99mTc label, 99mTc-PEG liposomes could be an attractive agent for infection or inflammation imaging.     

Correcting tumour SUV for enhanced bone marrow uptake: retrospective 18F-FDG PET/CT studies

PURPOSE: The concentration of F-FDG in the bone marrow is usually low. One common cause of high uptake is due to bone marrow stimulating drugs administered in conjunction with chemotherapy or radiation therapy. It has been hypothesized that the sequestration of F-FDG to the bone marrow may reduce the standardized uptake value (SUV) of a tumour. We tested this hypothesis by quantifying total F-FDG uptake in the bone marrow of patients with visibly enhanced bone marrow uptake and computing its effect on tumour SUV. METHODS: Total F-FDG in bone marrow was measured in two groups of PET/CT studies: one (n=19) with visibly enhanced bone marrow, the other (n=5), a baseline group with 'normal' levels of uptake. To measure the F-FDG in bone marrow, the entire skeleton in the CT was segmented from surrounding tissue, and the resulting volume applied to the PET image. Using kinetic analysis we show that the predicted correction factor to tumour SUV is given by (1-q0/Q)/(1-q/Q), where Q is the injected dose, and q and q0 are enhanced and baseline bone marrow uptake (MBq). RESULTS: The enhanced bone marrow uptake averaged 8.9+/-3.2% of injected dose (15.2% max) vs. 4.2+/-0.4% (4.6% max) at baseline. This resulted in a predicted artificial decrease in tumour SUV of up to 11.5% (4.9+/-4.3%, on average). CONCLUSION: Enhanced bone marrow uptake is predicted to reduce tumour SUVs by as much as 11.5% in our patient group and is a potential confounding factor in using SUV for monitoring tumour response to therapy.