Retrospective web-based multicenter evaluation of ¹8F-FDG-PET and CT derived predictive factors. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan in follicular non Hodgkin's lymphoma.

AIM: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan. PATIENTS, METHODS: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. RESULTS: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10±8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. CONCLUSION: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.

Physical aspects of scintigraphy-based dosimetry for nuclear medicine therapy.

In nuclear medicine therapy the treatment of tumours by radiation exposure from internally deposited labelled antibodies or labelled peptides is currently an active field of investigation. To permit the efficient delivery of high amounts of radiation dose to tumours while limiting the radiation dose to critical organs dosimetry calculations have to be performed. These are relying on scintigraphic data being input to the well known MIRD formalism. This paper focuses on the methods and the difficulties associated with the scintigraphic determination of organ kinetics. The physical properties of the well-known scintigraphic imaging modalities, PET, SPECT and planar scintigraphy, are discussed thereby taking into account the properties of the appropriate radionuclides currently being available for therapy and dosimetry. Several arguments are given and disputed for the limited clinical use of PET and SPECT in dosimetry and the ongoing preference of planar whole-body imaging as the method of choice. The quantitative restrictions still inherent to this method are also discussed in detail. Procedural recommendations are proposed covering all processes related to data acquisition, data correction and data analysis which finally lead to reliable estimations of organ dose.

[Radioimmunotherapy with yttrium-90 ibritumomab tiuxetan. Clinical considerations, radiopharmacy, radiation protection, perspectives]. / Radioimmuntherapie mit 90Y-markiertem Ibritumomab-Tiuxetan: Klinik, Radiopharmazie, Strahlenschutz, Perspektiven.

90Y-ibritumomab tiuxetan (Zevalin) is currently approved for radioimmunotherapy of patients with relapsed or refractory follicular non-Hodgkin's lymphoma pretreated with rituximab. Future directions are the combined use of 90Y-ibritumomab tiuxetan as part of the initial treatment and as first-line multi-agent therapy of relapsed disease. Current studies investigate patients with other than follicular indolent histologies, e. g. diffuse large cell lymphoma. Labelling of 90Y ibritumomab tiuxetan is a safe procedure, the radiochemical purity is not disturbed by a higher room temperature or by metallic impurity. Quality control is recommended by thin layer chromatography (TLC), strips >15 cm are favourable. TLC cannot distinguish between the correctly radiolabelled antibodies and radiocolloid impurity. If necessary, additional HPLC should be performed. Radiocolloid impurities are absorbed to the solid phase and do not reach the eluate. If the radiochemical purity test is insufficient (<95%), the additional cleaning using EconoPac 10 DG columns (Biorad, Hercules, CA, USA) is a reliable procedure to reduce the percentage of free radionuclide. However, this procedure is not part of the approval.

Chromogranin A: an additional tumor marker for postoperative recurrence and metastases of medullary thyroid carcinomas?

In this study, plasma concentrations of chromogranin A, calcitonin and carcinoembryonic antigen (CEA) were measured in 40 healthy volunteers as well as in 129 patients with recurrences and/or metastases of neuroendocrine tumors and of medullary thyroid carcinomas (MTCs). A double antibody assay was employed using polyclonal rabbit antibodies to a C-terminal fragment of the protein for detection of human chromogranin A. Using ROC analysis, a cutoff at 22 U/l chromogranin A was calculated. In patients with neuroendocrine tumours, much higher serum concentrations of chromogranin A than for patients with MTC (80% vs. 46%) were measured. The following sensitivities were found: chromogranin A; 46%, calcitonin 100%, CEA 52%. Furthermore, the mean values of chromogranin A concentrations correlated with the tumour mass and/or number of metastases in MTC and neuroendocrine tumours. Evaluation of follow-up studies remains to be completed; however, preliminary results showed similarities regarding the behaviour of chromogranin A and calcitonin. Despite the findings of this study, the observations could not confirm chromogranin A as a reliable marker for metastazing or recurrent MTC.

[Can immunoradiometric measurement of thyrotropin (TSH) in human serum compete with a luminometric assay?]. / Ist die immunradiometrische Bestimmung von Thyreotropin (TSH) im Humanserum einem Lumineszenzassay unterlegen?

UNLABELLED: The development of highly sensitive, nonradioimmunometric assays for the measurement of thyrotropin (TSH) during the last few years have improved the measurement of low TSH values and thus benefit the diagnosis of thyroid function disorders. These third or fourth generation assays are especially popular in laboratories not accustomed to the use of radioactive tracers and can be easily automatized. AIM: This study investigates whether these new assays provide an advantage in routine diagnosis of thyroid disorders. METHODS: TSH was measured in 150 patients with various thyroid pathology using an immunoradiometric assay (IRMA) as well as a highly sensitive luminometric assay (LUMI), both by B.R.A.H.M.S. Diagnostica. We used the current modern IRMA (available since 1997) TSH was below 0.4 mU/l, between 0.4 and 4.0 mU/l, and above 4.0 mU/l in a third of the patients in each group, respectively. RESULTS: As expected the results obtained with LUMI and IRMA correlated well for TSH values above 0.1 mU/l and less well between 0.1 and 0.01 mU/l. There was no correlation between the two types of assay at TSH concentrations below 0.01 mU/l. This shows that measurements using both types of assay become increasingly less precise below 0.1 mU/l. CONCLUSION: Both types of assay gave an identical estimate of thyroid function in every single patient. Use of the LUMI did not give additional information leading to a change in patient management. Therefore, TSH measurement using IRMA does still meet today's routine clinical requirements.

Accuracy of the intra-operative radioguided localization of the sentinel lymph node (SLN) 24 hours after lymphoscintigraphy in patients with malignant melanoma.

AIM: For optimized logistics for the sentinel lymphadenectomy (SL) it might be helpful for the clinics involved if a longer time period between the lymphoscintigraphy (LS) and surgery is possible. Therefore, we investigated if a precise localization of the sentinel lymph node is possible 24 hours after LS. METHODS: 78 patients with primary malignant melanoma (MM; n = 44) or with MM pre-operated by excisional biopsy (n = 34) were investigated. In 40 cases the tumor was localized on the trunk and in 38 cases on the extremities. Mean MM thickness was 2.68 mm (range: 0.29 to 12 mm). In all patients a lymphoscintigraphy (LS) with an average of 85 MBq of Tc-99m nanocolloid was performed one day prior to surgery. Immediately after tracer application dynamic data acquisition was started at a LFOV gamma camera followed by a whole body scan. With a hand-held gamma detector (C-Trak) 2, 4, 6, 8, and 24 hours after tracer administration the SLN was identified and the counts registered. RESULTS: 94 SLNs were identified in 87 lymphatic basins from which 86 could be resected. Nine MM showed two draining channels. After 24 hours 15.5% (as an average) of the initial counts could be measured in the SLN. The uptake in the SLN in pre-operated versus patients with primary tumor was statistically not significant (p = 0.4). In 16 cases (20.5%) the SLN was tumor positive. Four of those patients developed distant metastases and two died within the first year. None of the patients with negative SLN developed distant metastases or died. CONCLUSION: The remaining activity in the SLN up to 24 hours after administration is sufficient for their intra operative localization. The method of lymphoscintigraphy and localization of the SLN by a hand-held gamma detector optimizes the intra operative identification of the SLN in patients with malignant melanoma.

Persistent vegetative state: evaluation of brain metabolism and brain perfusion with PET and SPECT.

Patients in persistent vegetative state (PVS) after severe head trauma were investigated with 99mTc-ECD SPECT and 18F-FDG PET to further characterize the degree of brain damage and to obtain insight into changes of brain perfusion and glucose metabolism. 18F-FDG PET and 99mTc-ECD SPECT were performed in 16 patients in PVS. Quantitative PET data were compared with that obtained from seven normal controls. After spatial normalization into Talairach space, global grey matter values and regional data using predefined ROI sets were derived. For comparison of PET and SPECT, regional data were normalized to their individual mean grey matter values. Patients in PVS showed significantly lower values of cerebral glucose metabolism than did the controls. The mean reduction of grey matter values in cortical and subcortical structures was 58%, except in the vermis cerebelli, where only a reduction of 16% was found compared to the controls. Comparing the glucose metabolism and perfusion within the patient group, the pattern of both modalities was similar in the neocortex and internal ganglia. In the cerebellar hemispheres a relatively higher perfusion than glucose metabolism was found. The overall reduction of 58% of glucose metabolism in grey matter structures is in accordance with other PET studies investigating PVS patients with different disease histories. The relative preserved activity of vermis cerebelli seems to be an uncommon finding not described by other authors up to now.

Preparation and biodistribution of rhenium-188 labeled albumin microspheres B 20: a promising new agent for radiotherapy.

Intra-arterial infusion of labeled particles is an effective method for endoradiotherapy of tumors. In this study, we radiolabeled biodegradable HSA microspheres (mean diameter = 25 microm) with the short-lived beta-emitter 188Re available from the aluminia-based 188W/188Re generator system. After 1 h 35-40% of the relative large amount of Sn(II) chloride required for effective reduction of Re(VII) for efficient attachment to the particles is precipitated as an amorphous coat of tin hydroxid colloid on the particle surface. The final 188Re bound to the particles was found to be stable in vitro. The radiolabelling yield was > 90%. The biological half-life was > 250 h and demonstrated sufficient in vivo stability after i.v. injection in Wistar rats. Because of the attractive properties of 188Re and the uniform particle size and stability, in vivo, this new agent is an attractive candidate for endoradiotherapy of tumors after selective catheterization.

Contemporary issues in HIM. Wireless LANs.

Wireless LANs are a relatively new form of network whose popularity is growing rapidly. Although they probably will not completely replace wired networks, wireless LANs can fill several important niches in network applications. In this article, we looked at rationales for wireless LANs, discussed several broad categories of wireless applications, and described two transmission techniques currently dominant in wireless networks. We then reviewed several different wireless network structures and wireless hardware connections, and looked at ranges and transmission rates. The article closed with a presentation of some relevant considerations regarding wireless LANs.

Contemporary issues in HIM. Kerberos--security for sensitive data.

Kerberos is a software package designed to enhance distributed computing security through the use of computerized tickets. In this article, we have looked at Kerberos data elements and protocols, and illustrated their use in a small example system. This and other security measures will be necessary to ensure privacy of patient records in the future.

Input/output units.

I/O units span a broad range of sophistication. An elementary von Neumann implementation requires that the CPU directly controls the I/O unit. The CPU must repeatedly test the status of the device to see if the requested operation has been finished. A major advance in the design of the I/O unit was made possible by the addition of interrupts to the computer. This feature facilitated multiprogramming, with its associated increases in efficiency and productivity. In many applications today, large amounts of data must be transferred and many interrupts must be processed. The performance of the I/O unit in systems running these applications is critical. In transaction processing, for instance, the speed and efficiency of the I/O unit is more critical than the speed of the ALU.

Peripheral controllers and devices--Part 1.

In this article, we looked at several peripherals, described their characteristics, and described how they are connected to computers. We included some discussions of problems caused by electrical and mechanical differences between computers and peripheral devices. During the past few years, many companies have addressed such problems. Numerous standards have been defined as a result of this work. These standards specify everything from what type of connectors will be used to the timing of electrical signals. They make it easier for peripheral manufacturers to design their devices for a wide range of computers. Peripherals and their controllers are important components of any computer system. Sometimes, however, other parts of the system, such as the control unit and main memory, receive more attention. Many engineers want to design new processors, but shy away from the design of peripherals and controllers; they consider such designs less glamorous. In reality, designs for some peripherals and their controllers can be more challenging than the design of the CPU itself. A computer without peripherals is of little use, other than as a paper weight. Until we attach peripherals to the computer, none of its power is accessible to the user. Peripherals turn computers into useful tools.

The hardware components of a computer system.

The two goals of this article are to give you a very brief overview of the evolution of computing and an introduction to the elements of a computer. The birth of the modern computer can be traced to John von Neumann. The model he proposed consisted of four major parts: the control unit, the arithmetic unit, the memory, and the input/output unit. His concept for a "stored program" computer provided the foundation for five decades of computer designs.

Software: using the hardware.

This concludes our overview of system software. We have not included all parts of that software and have only briefly described the parts we did include. However, we hope that you now have an appreciation of the many, many things going on "underneath the surface" when you click a mouse button or type a command on your computer.

World of computers.

Being well informed on the latest computer terminology is a continuous challenge these days. In this article Pinkert and Wear give us a vocabulary lesson for computer consumers.

Software engineering tools.

We have looked at general descriptions and illustrations of several software development tools, such as tools for prototyping, developing DFDs, testing, and maintenance. Many others are available, and new ones are being developed. However, you have at least seen some examples of powerful CASE tools for systems development.

Operating system components--Part II.

To summarize this discussion, let us look at a prototype, a capsule scenario in an OS. You make a process creation request on your local timeshare system. The long-term scheduler queues up this request, and eventually creates the corresponding process. Your process takes its turns executing, scheduled by the short-term scheduler. You request a tape drive to retrieve some archived data you need, and thus invoke the resource manager. You use the file manager to access the archived data. You use the I/O system to interact with the application program and to print the reports. The memory manager is swapping pages of your data and program between main memory and secondary memory. The dispatcher in the kernel is loading your process context into the CPU when your process is next on the execute list. The interrupt handler in the kernel is servicing interrupt requests, such as those made when you do I/O to the tape. The concurrency control in the kernel is coordinating your updating and spooled printing activities. So, your process is invoking activities throughout the various layers of the OS. Most of the time, you are unaware of these many varied activities.

Computer networks.

We have looked at several aspects of networks in this article. As you read about networks, and use them, we hope our discussions will help you understand some of the associated concepts and terms. For instance, suppose someone describes an Ethernet installation as a bus topology LAN using the 1-persistent CSMA/CD protocol with horizontal cables on each floor connected by repeaters to a vertical cable backbone running from the basement to the roof. You now have seen what that description implies. To close this article, we ask you to refer back to Figure 1. Our sample network transfer from Marie to Lars was described as being accomplished through a number of layers or steps, most of which were transparent to the users. Building upon the material presented in this article, we can now give you a more detailed illustration of those layers. Figure 13 shows the seven layers in network model defined by the International Standards Organization, ISO: application, presentation, session, transport, network, data link, and physical. We do not have space here to discuss each layer in detail, but Figure 13 does give a typical operation that is done in each layer.

Reliable computer systems.

In this article, we looked at some decisions that apply to the design of reliable computer systems. We began with a discussion of several terms such as testability, then described some systems that call for highly reliable hardware and software. The article concluded with a discussion of methods that can be used to achieve higher reliability in computer systems. Reliability and fault tolerance in computers probably will continue to grow in importance. As more and more systems are computerized, people will want assurances about the reliability of these systems, and their ability to work properly even when sub-systems fail.

Contemporary issues in HIM. Costs of ownership.

Cost of ownership includes (among others) initial cost, cost of operation, cost of maintenance, and cost of training. Two important components of initial cost are the cost of design and the cost of manufacturing. In this article, we have looked at how factors other than initial cost affect the total cost of ownership of a product. We also discussed how trade-offs can affect performance and cost. Before making any decision on purchasing a complicated new system, the user needs to evaluate the total cost of ownership to determine which product to buy. Unfortunately, it is not always easy to find all the information needed to make these decisions.