The Reference Image Database to Evaluate Response to therapy in lung cancer (RIDER) project: a resource for the development of change-analysis software.

Critical to the clinical evaluation of effective novel therapies for lung cancer is the early and accurate determination of tumor response, which requires an understanding of the sources of uncertainty in tumor measurement and subsequent attempts to minimize their effects on the assessment of the therapeutic agent. The Reference Image Database to Evaluate Response (RIDER) project seeks to develop a consensus approach to the optimization and benchmarking of software tools for the assessment of tumor response to therapy and to provide a publicly available database of serial images acquired during lung cancer drug and radiation therapy trials. Images of phantoms and patient images acquired under situations in which tumor size or biology is known to be unchanged also will be provided. The RIDER project will create standardized methods for benchmarking software tools to reduce sources of uncertainty in vital clinical assessments such as whether a specific tumor is responding to therapy.

NCI Cancer Imaging Program efforts and their application to non-conventional radionuclides.

The US National Institute of Health (NIH) National Cancer Institute's Cancer Imaging Program funds research in cancer imaging. The article describes funding initiatives, such as Requests for Application and Program Announcement, funding mechanisms such as the R01 and R21, the Institutes of the NIH that fund imaging research, the application process, the application review process, and on-line resources to assist applicants for research funding for non-conventional radionuclides for imaging and therapy.

Future directions in small animal imaging.

The adaptation and development of imaging technologies for use in small animals has the potential to be a refinement with profound effects on how basic cancer research using animals is conducted. The authors describe how NCI funding is helping to advance research in this area.

National Cancer Institute initiative: Lung image database resource for imaging research.

Preliminary clinical studies suggest that spiral computed tomography (CT) of the lungs can improve early detection of lung cancer in high-risk individuals. More clinical studies are needed, however, before public health recommendations can be proposed for population-based screening. Spiral CT generates large-volume data sets and thus poses problems in terms of implementation of efficient and cost-effective screening methods. Image processing algorithms such as computer assisted diagnostic (CAD) methods have the potential to assist in lesion (eg, nodule) detection on spiral CT studies. CAD methods may also be used to characterize nodules by either assessing the stability or change in size of lesions based on evaluation of serial CT studies, or quantitatively measuring the temporal parameters related to contrast dynamics when using contrast material-enhanced CT studies. CAD methods therefore have the potential to enhance the sensitivity and specificity of spiral CT lung screening studies. Lung cancer screening studies now under investigation create an opportunity to develop an image database that will allow comparison and optimization of CAD algorithms. This database could serve as an important national resource for the academic and industrial research community that is currently involved in the development of CAD methods. The National Cancer Institute request for applications (RFA) (CA-01-001) has already been announced (April 2000) to establish and support a consortium of academic centers to develop this database, the consortium to be referred to as the Lung Image Database Consortium (LIDC). This RFA is now closed. Five academic sites have been selected to be members of the LIDC, the first meeting of this consortium is planned for spring of 2001, and a public meeting is to be held in 2002. This report is abstracted from the previously published RFA to serve as an example of how an initiative is developed by the National Cancer Institute to support a research resource. For specific details of the RFA, please access the following Internet site: http://www. nci.nih.gov/bip/NCI-DIPinisumm.htm#a11.

Labelling of Re-ABP with 188Re for bone pain palliation.

Etidronate and medronate have been labelled with technetium-99m (99mTc-HEDP, 99mTc-MDP) for bone scanning and, with rhenium-188 (188Re-HEDP) to palliate the pain resulting from bone metastases. The objective of this study was to label alendronate, ABP, a new bisphosphonate, with SnF2-reduced-188Re. The reagents for the 5 mg ABP kit were SnF2, KReO4 and gentisic acid at acid pH. The chemical, spectroscopic and microscopic characteristics, quality control, rat bone uptake of [188Re]Re-ABP and similarities with 99mTc-ABP are presented. We conclude that this is a promising new radiopharmaceutical for bone metastases pain palliation.

Study design in the evaluation of breast cancer imaging technologies.

RATIONALE AND OBJECTIVES: Bringing a new imaging technology to market is a complex process. Beyond conceptualization and proof of concept, obtaining U.S. Food and Drug Administration (FDA) approval for clinical use depends on the documented experimental establishment of safety and efficacy. In turn, safety and efficacy are evaluated in the context of the intended use of the technology. The purpose of this study was to examine a conceptual framework for technology development and evaluation, focusing on new breast imaging technologies as a highly visible and current case in point. MATERIALS AND METHODS: The FDA views technology development in terms of a preclinical and four clinical phases of assessment. With a concept of research and development as a learning model, this phased-assessment concept of regulatory review against intended use was integrated with a five-level version of a hierarchy-of-efficacy framework for evaluating imaging technologies. Study design and analysis issues are presented in this context, as are approaches to supporting expanded clinical indications and new intended uses after a new technology is marketed. CONCLUSION: Breast imaging technologies may be intended for use as replacements for standard-of-care technologies, as adjuncts, or as complementary technologies. Study designs must be appropriate to establish claims of superiority or equivalence to the standard for the intended use. Screening technologies are ultimately judged on their demonstrated effectiveness in decreasing cause-specific mortality through early detection, but they may be brought to market for other uses on the basis of lesser standards of efficacy (eg, sensitivity, specificity, positive and negative predictive value, and stage of disease detected).

Preparation and pharmacokinetics of samarium(III)-153-labeled DTPA-bis-biotin. Characterization and theoretical studies of the samarium(III)-152 conjugate.

The complex(153)Sm(III)DTPA-bis-biotin was prepared with a 99% radiochemical purity and a specific activity of 370 MBq/mg employing a molar ratio of DTPA-bis-biotin/Sm from 2 to 4 at pH 8.0. In vitro studies demonstrated that the complex is stable after dilution in saline and in human serum. Avidity of labeled biotin for avidin was not affected by the labeling procedure. Pharmacokinetic data of (153)Sm(III)DTPA-bis-biotin in normal mice showed that blood clearance is biexponential during the time interval from 0 to 24 h and that 3 h postinjection 92 +/- 4.32% of the dose is eliminated in the urine. To have further evidence which could sustain that (153)Sm(III)DTPA-bis-biotin is stable in solution as a real coordination complex, (152)Sm(III)DTPA-bis-biotin was obtained in macroscopic quantities and its characterization was done by IR, TGA, and conductivity measurements. The results indicated that the complex was chemically pure, where the Sm(3+) ion is neutralized by three carboxylate groups of the DTPA-bis-biotin ligand and coordinated to it. Using the Force Field method followed by ab initio calculations, the DTPA-bis-biotin and the Sm(III)DTPA-bis-biotin molecules were done. Accordingly, the coordination sphere of Sm(III) was totally satisfied with nitrogen and oxygen donors; the best coordination number was 9. The conformation geometry of both compounds is presented.

Preparation, biodistribution, and dosimetry of 188Re-labeled MoAb ior cea1 and its F(ab')2 fragments by avidin-biotin strategy.

The biotinylated monoclonal antibody (MoAb) ior cea1 and its F(ab')2 fragments were labeled with Re-188 by combination of avidin-biotin strategy. 188Re-MoAb, 188Re-MoAb-biotin, 188Re-F(ab')2, and 188Re-F(ab')2-biotin preparations were produced for these studies with specific activities of 1.30+/-0.18 GBq/mg and from instant freeze-dried kit formulations using ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand. There were no significant differences (p > 0.05) between the biodistribution in mice of biotinylated and unbiotinylated 188Re-labeled immunoconjugates. When avidin was injected as a chase after injection of 188Re-MoAb-biotin or 188Re-F(ab')2-biotin, the blood radioactivity level decreased approximately 75% (cumulated activity) and the effective dose decreased almost 25% with respect to that of the radioimmunoconjugates in which the chase effect was not used. Our results suggest that 188Re-labeled biotinylated MoAb ior ceal and its F(ab')2 fragments prepared by this method are stable complexes in vivo.

Antigens pre-bound to the primate erythrocyte complement receptor via cross-linked bispecific monoclonal antibody heteropolymers are rapidly cleared from the circulation.

We have used cross-linked, bispecific monoclonal antibody heteropolymers, specific for primate erythrocyte (E) complement receptor (CR1) and target antigen (Ag), to attach 125I-labeled Ag to 51Cr-labeled monkey erythrocytes (E) in vitro. Injection of these sensitized E into monkeys leads to rapid clearance from the circulation of several different 125I-labeled Ag with little, if any sequestration, lysis, or clearance of the E. It should now be possible, in principle, to use the heteropolymer-E system to facilitate the clearance of blood-borne pathogens from the circulation.

A noninvasive scintigraphic assessment of the colonic transit of nondigestible solids in man.

A noninvasive, scintigraphic technique for quantifying large intestinal transit time that provides low radiation doses was developed. The scintigraphic large intestinal transit (SLIT) method uses a total of 100 microCi of 111In encapsulated in ten 2-cm nondigestible capsules, which are ingested after a 6-hr fast. Two hundred fifty microcuries of 99mTc-sulfur colloid were given to outline the gastrointestinal tract. Images were acquired at 4-hr intervals until all capsules were excreted. Normal volunteers (n = 10) consumed a standardized diet 2 days prior and during imaging. Segmental transit times were measured in the following: ascending, transverse, descending, recto-sigmoid colons; hepatic and splenic flexures. The radiation absorbed dose to the large intestine for the SLIT technique is less than half of that associated with other radiographic methods of colonic transit time measurement.

Instrumentation and computers for brain single photon emission computed tomography.

Cerebral single-photon emission computed tomography (SPECT) requires attention to the instrumentation because of the anatomical location of the head at one end of the body, with a generally narrower diameter than the rest of the body. For a number of years, there have been SPECT units designed especially for head work, as well as general-purpose units that have performed well in imaging the head. The current emphasis on cerebral perfusion, using either agents that wash in and out with blood flow or agents that reflect blood flow in their static distribution, has allowed a concentration on imaging hardware and computer hardware and software for this purpose.

Lymphoscintigraphy and lymphedema of the lower extremities.

Lymphoscintigraphy, using technetium-99m-labeled sulphur microcolloid, was employed to study the flow and transport of lymph in the lower extremities of 39 consecutive patients in whom lymphedema of one or both legs was suspected clinically. Time-activity curves of four segments of each leg were evaluated for lymph capacity, flow and soft-tissue uptake, and compared with the results from film scintigraphy. Curve analysis provided quantitative evaluation of the extent of hypoplasia or aplasia in primary lymphedema and of lymphatic obstruction in secondary lymphedema, and is particularly suited to assess the involvement of lymphatics in chronic venous disease. Film scintigraphy, on the other hand, is preferable in cases in which the pattern of activity distribution in the affected extremity is diagnostic, such as in dermal back flow, traumatic lymphocele, or megalymphatics. Venography is most informative in cases of suspected underlying venous disease, but the role of lymphangiography, which shows only part of the lymphatic system and requires incision of the edematous tissues, is considered questionable.

Radiographic examination of the stomach and duodenum: comparison of single-, double- and biphasic-contrast methods.

We compared retrospectively three groups of 150 patients who had undergone radiologic examinations of the stomach and duodenum. Each group was examined with a different barium suspension and radiographic technique: single-contrast (SC), double-contrast (DC), or biphasic-contrast (BC). The radiographs of each study were evaluated for technical quality and visualization of lesions. The number of X-ray exposures, films, and the amount of fluoroscopic time for each study were tabulated. The total radiation dose and cost for each technique were calculated. The BC examinations required the greatest number of radiographic exposures and X-ray films; however, cost was highest for the DC method. Fluoroscopy was significantly longer during the DC procedures, and the total radiation dose was also highest with this technique. Gaseous distention and barium coating of the stomach were equally good for the BC and DC groups, but X-ray penetration of the barium suspension during compression filming was significantly better in the BC and SC groups. Areae gastricae were most frequently seen during the BC studies and artifacts from excess secretions, barium flocculation or gas bubbles were least commonly present using this technique. Significantly more lesions were demonstrated in the stomach with the BC technique than with the other methods; however, the number of lesions found in the duodenum was the same for each technique.

Estimation of 24-hour thyroid uptake of I-131 sodium iodide using a 5-minute uptake of technetium-99m pertechnetate.

The authors have developed a method to estimate the 24-hour sodium iodide thyroid uptake based on a 5-minute Tc-99m pertechnetate thyroid uptake using the equation: Estimated Iodide Uptake = 17.72*In(Pertechnetate Uptake) + 30.40. This estimation has a correlation coefficient of 0.90. It is based on a data pool of 44 patients who underwent I-131 and Tc-99m studies within 2 weeks of each other from 1978-1988, with established diagnoses as follows: 12 euthyroid, 6 hyperthyroid with multinodular goiters, 15 hyperthyroid with diffuse goiters, 4 with subacute thyroiditis, and 7 unknown. The population consisted of 30 women and 14 men with a mean age of 52.0 +/- 17.5 years; this sample was screened for use of thyroid hormone, propylthiouracil, and radiographic contrast. The authors believe this estimation method is of value whenever a 24-hour iodide uptake is desired, and where speed and minimizing radiation dose are factors. This method is strongly recommended for thyroid uptake evaluation before I-131 therapy.