Quantitative imaging test approval and biomarker qualification: interrelated but distinct activities.

UNLABELLED: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1.

The international measurement system for radionuclide metrology: A strategy for the future.

The Consultative Committee for Ionizing Radiation (CCRI) has coordinated the development of a long-term strategy to support the international measurement system for radionuclide metrology. Supported by the Bureau International des Poids et Mesures (BIPM) and its associated institutional members, the CCRI strategy captures how an NMI/DI can demonstrate capability in radionuclide metrology with the support that is available through the CCRI and the BIPM. The CCRI strategy, specifically the aspects with direct impact on radionuclide metrology, is described. Various projects to ensure that the international measurement system for radioactivity can be sustained in the short and long term will also be outlined.

NIST radiochemistry intercomparison program: a summary of four-year performance evaluation study. National Institute of Standards and Technology.

This paper summarizes the methods currently applied by the National Institute of Standards and Technology (NIST) for the preparation and verification of environmental and radiobioaasay performance evaluation materials for the traceability testing of low-level radioactivity measurements. The evaluation of measurement quality of the all participants indicated that over 90% of the intercomparison results complied with ANSI N42.22 and/or HPS N13.30 standards. Overall, the differences from the NIST values observed for all test nuclides and matrices are less than -7%, with a typical measurement precision better than 10% (1 s). The dependency of measurement quality on the test radionuclides, sample matrices, and radiochemical methods is identified by statistical analyses.

Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation.

In this study, a comparison of the effects of neutron and electron irradiation of aqueous DNA solutions was investigated to characterize potential neutron signatures in DNA damage induction. Ionizing radiation generates numerous lesions in DNA, including base and sugar lesions, lesions involving base-sugar combinations (e.g. 8,5'-cyclopurine-2'-deoxynucleosides) and DNA-protein cross-links, as well as single- and double-strand breaks and clustered damage. The characteristics of damage depend on the linear energy transfer (LET) of the incident radiation. Here we investigated DNA damage using aqueous DNA solutions in 10 mmol/l phosphate buffer from 0-80 Gy by low-LET electrons (10 Gy/min) and the specific high-LET (∼0.16 Gy/h) neutrons formed by spontaneous (252)Cf decay fissions. 8-hydroxy-2'-deoxyguanosine (8-OH-dG), (5'R)-8,5'-cyclo-2'-deoxyadenosine (R-cdA) and (5'S)-8,5'-cyclo-2'-deoxyadenosine (S-cdA) were quantified using liquid chromatography-isotope-dilution tandem mass spectrometry to demonstrate a linear dose dependence for induction of 8-OH-dG by both types of radiation, although neutron irradiation was ∼50% less effective at a given dose compared with electron irradiation. Electron irradiation resulted in an exponential increase in S-cdA and R-cdA with dose, whereas neutron irradiation induced substantially less damage and the amount of damage increased only gradually with dose. Addition of 30 mmol/l 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), a free radical scavenger, to the DNA solution before irradiation reduced lesion induction to background levels for both types of radiation. These results provide insight into the mechanisms of DNA damage by high-LET (252)Cf decay neutrons and low-LET electrons, leading to enhanced understanding of the potential biological effects of these types of irradiation.

Laboratories new to the ICRM.

The Scientific Committee of the ICRM decided, for the 2011 Conference, to present laboratories that are at a key developmental stage in establishing, expanding or applying radionuclide metrology capabilities. The expansion of radionuclide metrology capabilities is crucial to meet evolving and emerging needs in health care, environmental monitoring, and nuclear energy. Five laboratories (from Greece, Lithuania, Indonesia, Norway and Turkey) agreed to participate. Each laboratory is briefly introduced, and examples of their capabilities and standardization activities are discussed.

Radiation-based quantitative bioimaging at the national institute of standards and technology.

Building on a long history of providing physical measurements and standards for medical X rays and nuclear medicine radionuclides, the laboratory has expanded its focus to better support the extensive use of medical physics in the United States today, providing confidence in key results needed for drug and device development and marketing, therapy planning and efficacy and disease screening. In particular, to support more quantitative medical imaging, this laboratory has implemented a program to provide key measurement infrastructure to support radiation-based imaging through developing standard, benchmark phantoms, which contain radioactive sources calibrated to national measurement standards, to allow more quantitative imaging through traceable instrument calibration for clinical trials or patient management. Working closely with colleagues at the National Institutes of Health, Rensselaer Polytechnic Institute, the Food and Drug Administration and Cornell University, this laboratory has taken the initial steps in developing phantoms, and the protocols to use them, for more accurate calibration of positron emission tomography (PET) or single-photon emission computed tomography (SPECT) cameras, including recently standardizing (68)Ge. X-ray measurements of the laboratory's recently developed small, resilient and inexpensive length standard phantom have shown the potential usefulness of such a "pocket" phantom for patient-based calibration of computed tomography (alone or with PET) systems. The ability to calibrate diagnostic imaging tools in a way that is traceable to national standards will lead to a more quantitative approach; both physician and patient benefit from increased accuracy in treatment planning, as well as increased safety for the patient.