UNLABELLED:Fine-needle aspiration biopsy (FNAB) is inconclusive in up to 20% of patients with solitary thyroid nodules. In these cases, hemithyroidectomy is necessary, but only 20% of the nodules prove to be thyroid carcinoma. The aim of this study was to explore the potential of (18)F-FDG PET to reduce the number of unnecessary hemithyroidectomies in the preoperative assessment of thyroid nodules with inconclusive FNAB results.METHODS:Forty-four consecutive patients, scheduled for hemithyroidectomy because of inconclusive FNAB findings, participated in this prospective study. (18)F-FDG PET of the thyroid region was performed before hemithyroidectomy, and standardized uptake values were calculated. The final histopathologic diagnosis served as a standard of reference.RESULTS:Histopathologic examination of the surgical specimens revealed 7 well-differentiated thyroid carcinomas in 6 patients, all accumulating (18)F-FDG (negative predictive value, 100%). (18)F-FDG accumulated in 13 of 38 benign nodules. The pre-PET probability for cancer in this study population was 14% (6/44), and the post-PET probability increased to 32% (6/19). The percentage of unnecessary hemithyroidectomies in a hypothetical algorithm using (18)F-FDG PET was only 30% (13/44), compared with 86% (38/44) without (18)F-FDG PET. (18)F-FDG PET reduced the number of futile hemithyroidectomies by 66% (25/38) (95% confidence interval, 49%-80%; Fisher's exact test, P = 0.0038). Semiquantitative analysis using standardized uptake values did not help to further reduce this number.CONCLUSION:In addition to data in the literature demonstrating accurate detection of thyroid cancer by (18)F-FDG PET, this study showed that (18)F-FDG PET should play an important role in the management of patients with inconclusive cytologic diagnosis of a thyroid nodule. (18)F-FDG PET reduced the number of futile hemithyroidectomies by 66%. Although PET is a relatively costly procedure, this cost outweighs the costs and risks associated with unnecessary thyroid surgery.

UNLABELLED:The use of dynamic (18)F-FDG PET to determine changes in tumor metabolism requires tumor and plasma time-activity curves. Because arterial sampling is invasive and laborious, our aim was to validate noninvasive image-derived input functions (IDIFs).METHODS:We obtained 136 dynamic (18)F-FDG PET scans of 76 oncologic patients. IDIFs were determined using volumes of interest over the left ventricle, ascending aorta, and abdominal aorta. The tumor metabolic rate of glucose (MRGlu) was determined with the Patlak analysis, using arterial plasma time-activity curves and IDIFs.RESULTS:MRGlu using all 3 IDIFs showed a high correlation with MRGlu based on arterial sampling. Comparability between the measures was also high, with the intraclass correlation coefficient being 0.98 (95% confidence interval, 0.97-0.99) for the ascending aorta IDIF, 0.94 (0.92-0.96) for the left ventricle IDIF, and 0.96 (0.93-0.98) for the abdominal aorta IDIF.CONCLUSION:The use of IDIFs is accurate and simple and represents a clinically viable alternative to arterial blood sampling.

In three patients with catheter-associated candidaemia, use of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) led to the diagnosis of Candida lung abscesses, which was confirmed by computed tomography and a favourable response to antifungal therapy. It was concluded that FDG-PET is a promising new imaging technique that enables early identification of sites of disseminated candidiasis, and that this technique can be used in the evaluation of therapy.

PURPOSE:A study was designed to define the therapeutic efficacy, safety, and toxicity of two sequential high-dose treatments of radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell carcinoma. Here, we report the dosimetric analysis and the relationship between the development of a human antichimeric antibody response and altered pharmacokinetics. EXPERIMENTAL DESIGN:Patients (n = 29) with progressive metastatic renal cell carcinoma received a low dose (222 MBq) of [131I]cG250 for dosimetric analysis, followed by the first radioimmunotherapy with 2,220 MBq/m2 [131I]cG250 (n = 27) 1 week later. If no grade 4 hematologic toxicity was observed, a second low dose of [131I]cG250 (n = 20) was given 3 months later. Provided that no accelerated blood clearance was observed, a second radioimmunotherapy of [131I]cG250 was administered at an activity-dose level of 1,110 MBq/m2 (n = 3) or 1,665 MBq/m2 (n = 16). After each administration, whole-body images were obtained and the pharmacokinetics and the development of human antichimeric antibody responses were determined. Radiation-absorbed doses were calculated for whole body, red marrow, organs, and metastases. RESULTS:No correlation was found between hematologic toxicity and radiation-absorbed dose to the whole body or bone marrow, nor administered activity (MBq and MBq/kg). The tumor-absorbed doses varied largely. An inverse relation between tumor size and radiation-absorbed dose was found. Most tumor lesions received <10 Gy, whereas only lesions <5 g absorbed >50 Gy. A relatively high number of patients developed a human antichimeric antibody response (8 of 27) with altered pharmacokinetics, hampering additional radioimmunotherapies in four of these patients. CONCLUSIONS:Dosimetric analysis did not adequately predict the degree of bone marrow toxicity. When human antichimeric antibody developed, the rapid clearance of radioactivity from the blood and body prohibited further treatment. According to the calculated absorbed dose in metastatic lesions, future radioimmunotherapy studies with radiolabeled cG250 should aim at treatment of small-volume disease or treatment in an adjuvant setting.

UNLABELLED:Radiolabeled leukotriene B4 (LTB4) antagonist DPC11870 is able to reveal infectious and inflammatory foci in distinct animal models. Because previous studies showed that accumulation of (111)In-DPC11870 in the abscess continued although the tracer had cleared from the circulation, we decided to investigate the pharmacodynamics of (111)In-DPC11870 and determine the mechanism of accumulation of the radiolabeled LTB4 antagonist in the abscess.METHODS:(111)In-DPC11870 was intravenously injected in healthy New Zealand White rabbits and rabbits with intramuscular Escherichia coli infection. Pharmacodynamics were studied by serial imaging and by ex vivo counting of dissected tissues. The mechanism of visualization of the abscess was investigated in rabbits with intramuscular infection that was induced 16 h after intravenous administration of (111)In-DPC11870. In addition, heterologous leukocytes and bone marrow cells of a donor rabbit were labeled with (111)In-DPC11870 in vitro and the biodistribution of these in vitro radiolabeled cells was compared with that of (111)In-DPC11870 in rabbits with an infection.RESULTS:The LTB4 antagonist (111)In-DPC11870 revealed the intramuscular abscess in rabbits only a few hours after injection. Quantitative analysis of the images confirmed accumulation of (111)In-DPC11870 in the abscess although the compound had cleared almost completely from the circulation. Radioactivity concentration in the bone marrow decreased more rapidly in infected animals than in healthy animals. Therefore, we hypothesized that (111)In-DPC11870 associates with receptor-positive (bone marrow) cells and accumulated in the abscess because of subsequent migration from the bone marrow to the abscess. Accumulation of radioactivity in the abscess induced 16 h after (111)In-DPC11870 injection was similar to that in animals intravenously injected with the tracer 24 h after induction of the abscess (0.37 +/- 0.16 percentage injected dose [%ID]/g). Moreover, differences in radioactivity concentration in the bone marrow of healthy and infected animals (0.67 +/- 0.29 %ID/g and 0.15 +/- 0.03 %ID/g at 24 h, respectively, after injection) supported our hypothesis. Additional studies with peripheral blood leukocytes and bone marrow cells that were labeled ex vivo with (111)In-DPC11870 showed the ability of these cells to migrate to the abscess (0.40 %ID/g and 0.52 %ID/g for (111)In-DPC11870 bone marrow cells and (111)In-DPC11870 peripheral blood leukocytes, respectively, 24 h after injection).CONCLUSION:The (111)In-labeled LTB4 antagonist DPC11870 accumulates in infectious and inflammatory foci because of binding to LTB4 receptors expressed on activated hematopoietic cells that subsequently migrate to the site of infection, which leads to visualization of the infectious lesions.

UNLABELLED:Timely identification of metastatic complications of bloodstream infections due to spreading of the microorganisms to distant sites, although critical, is often difficult. As 18F-FDG accumulates in activated leukocytes in infectious lesions, 18F-FDG PET represents a promising imaging technique in these patients. The aim of this study was to assess the value of 18F-FDG PET in detecting infectious foci in patients at high risk of metastatic complications.METHODS:The results of all 18F-FDG PET scans ordered because of suspected metastatic infection from October 1998 to September 2004 were analyzed retrospectively. These results were compared with conventional investigation techniques and the final clinical diagnosis.RESULTS:The results of 40 18F-FDG PET scans were evaluated. In 60% of all episodes, Gram-positive bacteria were cultured, in 18% Gram-negative bacteria, in 20% Candida spp., and in 3% the infection was polymicrobial. Metastatic complications were diagnosed in 75% of all episodes. A median number of 4 diagnostic procedures to search for metastatic infection had been performed before 18F-FDG PET was ordered. 18F-FDG PET diagnosed a clinically relevant new focus in 45% of cases and confirmed abnormalities already diagnosed in 30% of cases. The positive predictive value of 18F-FDG PET was 91% and the negative predictive value was 100%.CONCLUSION:18F-FDG PET is a valuable imaging technique in patients at high risk of metastatic infectious disease, even when the results of other diagnostic procedures are normal.

UNLABELLED:Previous studies have shown that pretargeting allows rapid visualization of renal cell carcinomas (RCC) with an (111)In-labeled bivalent peptide. For radioimmunotherapy, a beta-emitting radionuclide labeled to a bivalent peptide is required. Therapeutic efficacy of these radionuclides depends on the E(max), physical half-life, and residence time of the radiolabel in the tumor. The (131)I radiolabel generally clears rapidly from the tumor after internalization and subsequent degradation of the bivalent l-amino acid peptide (l-a.a. peptide) in the tumor cells. To improve the residence time of the iodine label in the tumor, a new bivalent peptide was synthesized that is peptidase resistant and consists of 4 d-amino acids (d-a.a. peptide). Here we investigated the characteristics of the residualizing iodine label in SK-RC-52 RCC tumors.METHODS:The d-a.a. peptide was manually synthesized according to standard solid-phase Fmoc/HBTU (2-[1H-benzotriazole-1-yl]-1,1,3,3-tetramethyluronium hexafluorophosphate) chemistry. The uptake and retention in the tumor of (111)In-/(125)I-labeled bivalent peptides (l-a.a. peptide and d-a.a. peptide) were studied in female BALB/c athymic mice with subcutaneous SK-RC-52 RCC tumors. Tumors were pretargeted with the bispecific monoclonal antibody (bs-mAb) G250xDTIn-1 and, 72 h later, mice were injected intravenously with one of both radiolabeled peptides. The effect of bs-mAb-diDTPA-bs-mAb (DTPA is diethylenetriaminepentaacetic acid) bridging at the tumor cell surface on the internalization of the bs-mAb-diDTPA complex was investigated in SK-RC-52 tumor-bearing mice.RESULTS:The maximum uptake and retention of (125)I-labeled l-a.a. peptide in the tumor were significantly lower compared with that of the (111)In-labeled l-a.a. peptide. In contrast, the tumor uptake and retention of the (125)I-labeled d-a.a. peptide) were similar to that of the (111)In-labeled l-a.a. peptide but were superior at later time points. The biodistribution of the radioiodinated d-a.a. peptide was highly similar to that of the (111)In-labeled d-a.a. peptide, and both radiolabeled peptides were retained significantly better in the tumor than the (111)In-labeled l-a.a. peptide. bs-mAb-diDTPA-bs-mAb bridge formation did not affect internalization of the bs-mAb-diDTPA complex.CONCLUSION:Uptake and retention in the tumor of the iodinated peptide after pretargeting with a bs-mAb can be significantly improved using d-a.a. peptides. Accordingly, the radiation dose to the tumor, correlating with the therapeutic efficacy of pretargeted RCC, can be enhanced substantially.

OBJECTIVE:The aim of this study was to compare the dynamic distribution of fluorodeoxyglucose (FDG) in malignant and in infectious lesions.METHODS:The dynamic distribution of FDG was studied in Rowett nude (RNU) rats with a LS174T carcinoma xenograft in the left front leg and an Escherichia coli-induced focal infection in the right front leg. In 5 rats, dynamic FDG-PET was performed (27 frames of 6-15 minutes) up to 4 hours after injection of 11 MBq 18FDG. The mean FDG uptake (SUV) was calculated and plotted by using a region of interest (ROI) centered over both lesions. In groups of 6 rats, the biodistribution of FDG was determined by counting dissected tissues at 1, 2, 3, and 4 hours after an injection of 11 MBq FDG. Means +/- the standard error of the mean (SEM) were calculated.RESULTS:Dynamic positron emission tomography (PET) visualized both the tumor and the infection. The ROI analysis showed that FDG uptake in the infections was faster and higher, as compared to the tumor lesions. FDG uptake in the tumor reached a standardized uptake value (SUV) of 0.8 +/- 0.3 at 60 minutes and in the infectious lesions a SUV of 1.6 +/- 0.2 at 45 minutes, both remaining constant until 4 hours postinjection (p.i.). In the biodistribution study with ex vivo tissue counting, FDG had accumulated up to 1.1 +/- 0.1 %ID/g and 0.8 +/- 0.1 %ID/g at 1 hour in the tumor and infection, respectively, and remained constant until 4 hours for both lesions without significantly different wash-out from the 2 lesions. The tumor/blood and abscess/ blood ratios increased with time to 57 +/- 17 and 48 +/- 14, respectively.CONCLUSION:Although in this model differences in absolute FDG uptake and initial kinetics between tumor and infection were observed, the wash-out rate of FDG from the lesions was similar over time. The retention of FDG in the inflammatory lesion indicated that dual time-point imaging does not necessarily resolve diagnostic pitfalls for FDG-PET in oncology in order to discriminate between malignant tumorous and benign infectious lesions.

In previous studies we demonstrated that lipophilic (99m)Tc-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clearance of three hydrophilic analogues of 1. Divalent LTB4 antagonist 17 (DPC11870-11) is a DTPA conjugate for radiolabeling with In-111. Monovalent LTB4 antagonists 15 (BMS57868-88) and divalent LTB4 antagonist 18 (BMS57868-81) are conjugated to bifunctional chelator HYNIC for radiolabeling with (99m)Tc. The three compounds labeled efficiently with 111In or (99m)Tc with high radiochemical purity and specific activities. Scintigraphic images obtained in New Zealand White rabbits having acute intramuscular E. coli infection demonstrated that all agents were able to clearly visualize the abscess, and clearance was exclusively renal. The biodistribution of the (99m)Tc-labeled LTB4 antagonists was affected by the coligands used with the HYNIC chelator and by the monovalent or divalent nature of the receptor binding moiety. The best scintigraphic images were obtained with monovalent HYNIC conjugate 15 using tricine and isonicotinic acid as coligands with HYNIC for coordination with (99m)Tc.

Purpose: The aim of these studies was to develop a pretargeting strategy for CEA-expressing cancers using biologically produced bispecific monoclonal antibodies (bsMAb). The bsMAbs used in this system have affinity for the carcinoembryonic antigen on the one hand, and for indium-labeled diethylenetriaminepentaacetic acid (DTPA), on the other.Experimental Design: Stable quadroma clones producing bsMAb MN-14xDTIn-1 were isolated. LS174T tumor - bearing mice were injected with 1 to 100 mu g of bsMAb followed by 1 to 60 ng of an In-111-labeled bivalent peptide [Ac-Phe-Lys(DTPA)-Tyr-Lys(DTPA)-NH2]. Mice were killed at 24 hours postinjection and the biodistribution of the radiolabel was determined. The biodistribution of diDTPA labeled with four different radionuclides (In-111, Tc-99m, nonresidualizing I-125, and residualizing I-125) was determined at various time points postinjection following pretargeting of LS174T tumors with bsMAb MN-14xDTIn-1.Results: Optimal tumor targeting was observed when tumors were pretargeted with 10 mu g of bsMAb MN-14xDTIn-1 and when 6 ng of a radiolabeled peptide was given 72 hours later. The uptake of the four radiolabels in LS174T tumors at 4 hours postinjection was similar. However, at later time points, the In-111-label and residualizing 125 I-label were better retained in the tumor than the nonresidualizing 125I label. Although the absolute uptake in the tumor (in terms of percentage of injected dose per gram of tissue) was 5-fold lower than the uptake obtained with directly labeled MN-14, the pretargeting strategy revealed much higher tumor-to-blood ratios due to the rapid clearance of the radiolabel from the circulation as compared with In-111-MN-14 (445 +/- 90 and 5.3 +/- 1.1, respectively, at 72 hours postinjection).Conclusions: Effective targeting of carcincoembryonic antigen - expressing tumors was achieved with a newly produced bispecific antibody. The In-111-labeled L-amino acid peptide and I-125-D-amino acid peptide were better retained in the tumor than the Tc-99m- and I-125-L-amino acid peptide. Very high tumor-to-blood ratios were obtained due to rapid background clearance.

UNLABELLED Studies have demonstrated that the bivalent (111)In-labeled leukotriene B4 (LTB4) antagonist DPC11870 reveals infectious and inflammatory lesions in various rabbit models. The radioactive tracer accumulates quickly at the site of infection and clears rapidly from the circulation, resulting in high-quality images. In this study, 2 new hydrazinonicotinamide (HYNIC)-conjugated compounds that are structurally related to DPC11870 were studied to further improve image quality. METHODS A bivalent HYNIC-conjugated LTB4 antagonist (MB81) and a monovalent one (MB88) were labeled with (99m)Tc. The radiolabeled compounds were intravenously injected into New Zealand White rabbits with E. coli infection in the left thigh muscle. The imaging characteristics of both compounds were compared with those of the bivalent (111)In-labeled LTB4 antagonist. RESULTS Both (99m)Tc-labeled LTB4 antagonists revealed the abscess from 2 h after injection onward. Abscess uptake at 8 h after injection was similar for both compounds (0.22 +/- 0.08 percentage injected dose per gram [%ID/g] and 0.36 +/- 0.13%ID/g for the bivalent and monovalent compounds, respectively). However, visualization of the abscess and the quality of the images were better after injection of MB88 than after injection of either of the bivalent LTB4 antagonists. The excellent delineation of the abscess by MB88 was mainly due to the more rapid clearance of this compound from nontarget organs. CONCLUSION The (99m)Tc-labeled HYNIC conjugated LTB4 antagonists MB88 and MB81 revealed infectious foci in rabbits within a few hours after injection. Imaging characteristics of monovalent (99m)Tc-MB88 were superior to those of the bivalent LTB4 antagonists DPC11870 and MB81. Therefore, of the 3 LTB4 antagonists, the monovalent LTB4 antagonist MB88 is the most potent and promising agent for visualizing and evaluating infection and inflammation in patients.

We have developed an efficient pretargeting strategy for renal cell carcinoma (RCC) based on a biologically produced bispecific monoclonal antibody (bs-mAb). Tumor targeting with this 2-step pretargeting strategy in the NU-12 mouse RCC model was very efficient compared with other pretargeting strategies, possibly due to unique characteristics of the NU-12 tumor used in our studies. Here we describe the bs-mAb G250xDTIn-1 pretargeting strategy in 3 different RCC nude mouse models. Methods: Three different human RCC xenografts in nude mice (NU-12, SK-RC-1, and SK-RC-52 tumors) were pretargeted with 100 pmol bs-mAb G250xDTIn-1. Three days after administration of the bs-mAb, mice were injected intravenously with 4 pmol In-111-labeled bivalent peptide, diDTPA-FKYK (DTPA is diethylenetriaminepentaacetic acid). At 1, 4, 24, 48, and 72 h after injection of the radiolabeled peptide, the biodistribution of the radiolabel was determined. The 3 RCC tumors were characterized in vivo and in vitro for G250 antigen expression, vessel density, vascular volume, and vascular permeability and by targeting with In-111-/(125)l-labeled cG250 mAb. Results: Using the pretargeting strategy, relatively high uptake of the radiolabel was observed in all 3 tumor models (maximum uptake: SK-RC-1 [278 +/- 130 %ID/g (percentage injected dose per gram), 1 h after injection) > NU-12 (93 +/- 41 % ID/g, 72 h after injection] > SK-RC-52 [54 +/- 9 %ID/g, 4 h after injection]). Remarkably, uptake of the radiolabel in the tumor did not correlate with G250 antigen expression. The kinetics of the radiolabel in the tumor varied largely in the 3 RCC tumors: SK-RC-1 and SK-RC-52 tumors showed a washout of the In-111 label from the tumor with time: only 30% of the radiolabel was retained in the tumor 3 d after injection, whereas the In-111 label was fully retained in NU-12 tumors. Physiologic characteristics (vessel density, vascular volume, and vascular permeability) of the tumors may explain these differences. Conclusion: G250 antigen- expressing tumors can be pretargeted very efficiently with the bs-mAb G250xDTIn-1. There was no correlation between G250 antigen expression and uptake of the radiolabel in the tumor using the pretargeting strategy or with directly labeled mAbs. Therefore, these studies show that physiologic characteristics of the tumor, such as vascular permeability, play a significant role in pretargeting.

UNLABELLED:Radiolabeled chemotactic peptides have been studied for their applicability to the visualization of infectious and inflammatory foci. Because a radiolabeled leukotriene B4 (LTB4) antagonist allowed visualization of intramuscular E. coli abscesses in rabbits within a few hours after injection, we decided to test the imaging characteristics of this agent in a more clinically relevant model of pulmonary aspergillosis. The pharmacokinetics and imaging characteristics of the 111In-labeled LTB4 antagonist DPC11870 were studied in New Zealand White rabbits with experimental pulmonary aspergillosis infection. The imaging characteristics of 111In-DPC11870 were compared with those of 67Ga-citrate, a radiopharmaceutical commonly used to detect pulmonary infections in patients.METHODS:Pulmonary aspergillosis was induced in the left lung of rabbits by intratracheal inoculation of 1 x 10(8) conidia of Aspergillus fumigatus. Three days after the inoculation, the rabbits received 111In-DPC11870 or 67Ga-citrate intravenously. Images were acquired at several time points up to 24 h after injection.RESULTS:Pulmonary aspergillosis was visualized with both agents. Images acquired after injection of 111In-DPC11870 showed uptake in the pulmonary lesions from 6 h after injection. Because of accumulation at the site of infection and clearance from the background, the images improved with time. Region-of-interest analysis at 24 h after injection revealed infected lung-to-normal lung ratios of 5.0 +/- 1.5 for 111In-DPC11870 and 2.9 +/- 0.6 for 67Ga-citrate.CONCLUSION:The radiolabeled LTB4 antagonist DPC11870 clearly delineated experimentally induced pulmonary aspergillosis in rabbits. Images acquired at 24 h after injection of 111In-DPC11870 were superior to those obtained after injection of 67Ga-citrate.

Vasculitis is a serious condition characterized by inflammation and necrosis of the blood vessel walls. Early and accurate assessment is important for successful management; however, diagnosis can be complicated by the absence of specific symptoms and signs, the limited specificity of biochemical tests, and the limitations of conventional imaging techniques in detecting frequently subtle vessel abnormalities. Although the American College of Rheumatology 1990 criteria for the classification of vasculitis are considered the gold standard for diagnosing vasculitis ( 1 Hunder G.G. Arend W.P. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Introduction. Arthritis Rheum. 1990; 33: 1065-1067 Crossref PubMed Scopus (615) Google Scholar , 2 Bloch D.A. Michel B.A. Hunder G.G. et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods. Arthritis Rheum. 1990; 33: 1068-1073 Crossref PubMed Scopus (217) Google Scholar , 3 Lie J.T. Illustrated histopathologic classification criteria for selected vasculitis syndromes. American College of Rheumatology Subcommittee on Classification of Vasculitis. Arthritis Rheum. 1990; 33: 1074-1087 Crossref PubMed Scopus (414) Google Scholar , 4 Lightfoot Jr, R.W. Michel B.A. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Arthritis Rheum. 1990; 33: 1088-1093 Crossref PubMed Scopus (937) Google Scholar , 5 Masi A.T. Hunder G.G. Lie J.T. et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). Arthritis Rheum. 1990; 33: 1094-1100 Crossref PubMed Scopus (1768) Google Scholar , 6 Leavitt R.Y. Fauci A.S. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. 1990; 33: 1101-1107 Crossref PubMed Scopus (1650) Google Scholar , 7 Calabrese L.H. Michel B.A. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of hypersensitivity vasculitis. Arthritis Rheum. 1990; 33: 1108-1113 Crossref PubMed Scopus (231) Google Scholar , 8 Mills J.A. Michel B.A. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of Henoch-Schonlein purpura. Arthritis Rheum. 1990; 33: 1114-1121 Crossref PubMed Scopus (770) Google Scholar , 9 Hunder G.G. Bloch D.A. Michel B.A. et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990; 33: 1122-1128 Crossref PubMed Scopus (2038) Google Scholar , 10 Arend W.P. Michel B.A. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990; 33: 1129-1134 Crossref PubMed Scopus (1719) Google Scholar , 11 Fries J.F. Hunder G.G. Bloch D.A. et al. The American College of Rheumatology 1990 criteria for the classification of vasculitis. Summary. Arthritis Rheum. 1990; 33: 1135-1136 Crossref PubMed Scopus (257) Google Scholar ), diagnosis and assessment of the extent and location of the disease is often difficult or sometimes impossible. In a study of 198 patients suspected of vasculitis, these criteria were not effective in diagnosing specific types of vasculitis ( 12 Rao J.K. Allen N.B. Pincus T. Limitations of the 1990 American College of Rheumatology classification criteria in the diagnosis of vasculitis. Ann Intern Med. 1998; 129: 345-352 Crossref PubMed Scopus (292) Google Scholar ).

Lipodystrophy is accompanied by increased adipose tissue inflammatory activity. Together with mitochondrial toxicity of nucleoside reverse transcriptase inhibitors, this induces metabolic stress causing increased glucose uptake. We hypothesized that this might be visualized by F-18-fluorodeoxyglucose positron emission tomography. Markedly increased subcutaneous F-18-fluorodeoxyglucose uptake was observed in three out of four HIV-infected patients with lipodystrophy on highly active antiretroviral therapy, but was absent in HIV-infected controls without lipodystrophy, making this an appropriate tool to visualize lipodystrophy.

UNLABELLED:The CXC chemokines are a family of closely related chemoattractant cytokines that bind to, attract, and activate neutrophils to variable degrees. In this study, the relationship between neutrophil-binding affinity and suitability for infection imaging was investigated in a selected group of CXC chemokines. Neutrophil-activating peptide-2 (NAP-2, 70 residues; also called CXCL7) binds with high affinity to the CXCR2 receptor on neutrophils. Recently, C-terminally truncated NAP-2-variants have been described that have enhanced neutrophil-binding affinity and neutrophil-stimulating capacity. Here, NAP-2 and its C-terminal shortened variants NAP-2(1-68), NAP-2(1-66), and NAP-2(1-63) were labeled with (99m)Tc via the hydrazinonicotinamide (HYNIC) chelator and their potential for imaging of infection was investigated in a rabbit model of infection. The CXC chemokine interleukin-8 (IL-8) was used for comparison. In addition, a series of (99m)Tc-labeled CXC chemokines were screened for their potential to image infection, including CTAP-III, GCP-2, ENA-78, PF-4, and IP-10.METHODS:The receptor-binding affinity of HYNIC-conjugated NAP-2 and its analogs was compared in competitive binding assays on Jurkat cells transfected with the CXCR2 receptor gene. Biodistribution of labeled NAP-2 (analogs) and other CXC chemokines in rabbits with intramuscular Escherichia coli infections was determined both by gamma-camera imaging and by counting dissected tissues at 6 h after injection.RESULTS:The CXCR2-binding affinity of the HYNIC-conjugated NAP-2 analogs relative to NAP-2 was as follows: NAP-2(1-68), 2.5-fold; NAP-2(1-66), 10-fold; and NAP-2(1-63), 3-fold. In the rabbit model, uptake in the abscess (in percentage injected dose per gram +/- SEM) was 0.084 +/- 0.015 for NAP-2, 0.098 +/- 0.010 for NAP-2(1-68), 0.189 +/- 0.044 for NAP-2(1-66), and 0.114 +/- 0.017 for NAP-2(1-63) at 6 h after injection. In comparison, higher uptake in the abscess was found for labeled IL-8, a modest uptake was found for GCP-2 and ENA-78, and a low uptake was found for CTAP-III, PF-4, and IP-10.CONCLUSION:This study showed a clear relationship between affinity to receptors on neutrophils and suitability for infection imaging. Of the NAP-2 variants, NAP-2(1-66) combined highest affinity to CXCR2 with the best characteristics for imaging. IL-8 binds to both CXCR1 and CXCR2 with high affinity and showed a superior imaging quality. The other CXC chemokines tested bind to neutrophils with lower affinity and were shown to be less suitable for infection imaging in this study.

Background: In patients with lung cancer, positron emission tomography (PET) using fluor-18-fluorodesoxyglucose (FDG) may be used both to detect extrathoracic metastases (ETM) and for mediastinal lymph node staging (MLS), potentially reducing the need for mediastinoscopy. We assessed the added value of FDG-PET in detecting ETM and focused on the reliability of FDG-PET and mediastinoscopy for MLS. Patients and methods: In 72 consecutive patients with non-small cell lung cancer, the impact of adding FDG-PET to full conventional clinical staging was prospectively analyzed. The predictive value of FDG-PET findings and tumor location for pathologic mediastinal lymph node status were assessed in a logistic regression analysis. Results: Unexpected extrathoracic metastases were detected by FDG-PET in 15% of patients. In MLS overall negative and positive predictive values were 71 and 83% for FDG-PET, and 92 and 100% for mediastinoscopy. However, the negative predictive value of FDG-PET was only 17% in case of FDG-PET positive N1 nodes and/or a centrally located primary tumor, whereas it was 96% in case of FDG-PET negative N1 nodes and a non-centrally located primary tumor. Conclusion: By incorporating FDG-PET in clinical staging, 15% of patients with lung cancer are upstaged due to unexpected extrathoracic metastases. In case of a negative mediastinal FDG-PET, mediastinoscopy can only be omitted in the presence of a non-centrally located primary tumor and without FDG-PET positive N1 nodes.