Harmonization of United States, European Union and Canadian First-in-Human Regulatory Requirements for Radiopharmaceuticals-Is This Possible?

In recent years, several new radiotracers and radionuclide therapies have been developed. There is a renaissance in nuclear medicine and molecular imaging today, for example, in terms of the ability to image and treat neuroendocrine and prostate malignancies. In order to be able to bring a new drug product from bench to bedside and assist patients, while also ensuring patient safety, stringent regulations must be met. However, differences in regulatory requirements, often based on jurisdictional politics rather than scientific evidence, can hinder global co-operation, increase expense, and slow progress. In an effort to rise above these differences, nuclear medicine advocacy organizations, regulators, and international agencies have begun to identify commonalities in the regulations to achieve harmonization. Indeed, a more streamlined approach to radiopharmaceutical drug development across jurisdictions could be achieved through establishing harmonized requirements for pre-clinical studies and manufacturing standards. This paper provides an educational overview of the regulatory and submission requirements governing investigational radiopharmaceuticals for first-in-human radiopharmaceuticals across the European and North American continents. It is hoped that through ongoing collaboration, regulatory reform and harmonization can become a reality and speed access to the most up-to-date evidence-based patient care for all.

ASSESSMENT OF EFFECTIVE DOSE FROM CONE BEAM CT IMAGING IN SPECT/CT EXAMINATION IN COMPARISON WITH OTHER MODALITIES.

The aim of this study was to assess radiation dose from the cone beam computed tomography (CBCT) component of single photon emission tomography/computed tomography (SPECT/CT) examinations and to compare it with the radiopharmaceutical related dose as well as dose from multidetector computed tomography (MDCT). Effective dose (ED) from computed tomography (CT) was estimated using dose-length product values and anatomy-specific conversion factors. The contribution from the SPECT component was evaluated using ED per unit administered activity for the radiopharmaceuticals listed in the International Commission on Radiological Protection Publications 80 and 106. With the exception of cardiac studies (0.11 mSv), the CBCT dose (3.96-6.04 mSv) was similar to that from the radiopharmaceutical accounting for 29-56 % of the total ED from the examination. In comparison with MDCT examinations, the CBCT dose was 48 and 42 % lower for abdomen/pelvis and chest/abdomen/pelvis scans, respectively, while in the chest the CBCT scan resulted in higher dose (23 %). Radiation dose from the CT component should be taken into consideration when evaluating total SPECT/CT patient dose.

JOURNAL CLUB: CT dose optimization for whole-body PET/CT examinations.

OBJECTIVE. The objective of this study was to optimize CT protocols for whole-body PET/CT by reducing radiation dose while minimizing effects on image quality. MATERIALS AND METHODS. Before protocol optimization, a survey of 140 consecutive patients was conducted to establish the baseline dose from a whole-body PET/CT examination. Another sample of 100 patients was surveyed to evaluate the reduction of radiation dose after implementation of the new protocol. Effective dose from the CT component of the examination was estimated using dose-length product (DLP) values from reports generated by the scanner and anatomy-specific conversion factors. Twenty-six patients who underwent studies before and after the optimization were included in an analysis of image quality. All 26 patients had maintained the same weight between the examinations and were scanned in the same position using a similar technique except for the changes made for CT dose optimization. The studies were randomized and blinded for an experienced PET and CT reader who graded the imaging quality of anatomic structures. RESULTS. CT protocol optimization resulted in a 32% reduction of the mean CT radiation dose: The mean effective dose was reduced from 8.1 to 5.5 mSv. The blinded analysis of image quality showed no clinically significant degradation of the lower-dose studies. The only structures visualized statistically better on the higher-dose CT scans were the carotid arteries and the region of the posterior triangle. CONCLUSION. The results of this study showed that optimization of CT acquisition can effectively reduce radiation dose in a whole-body PET/CT examination without significantly sacrificing image quality.

Microsatellite markers in the western prairie fringed orchid, Platanthera praeclara (Orchidaceae).

PREMISE OF THE STUDY: Primers for 31 microsatellite-containing loci were developed for the threatened orchid Platanthera praeclara to enable characterization of the population genetics of this tallgrass prairie native. • METHODS AND RESULTS: Sixteen polymorphic microsatellite loci were identified from four populations. Six of these loci were not in linkage disequilibrium. The average number of alleles per locus per population ranged from 6.4 to 8.9. • CONCLUSIONS: The results indicate that six of the polymorphic loci will be useful in future studies of population structure, gene flow, and genetic diversity.

The establishment of genetically engineered canola populations in the U.S.

Concerns regarding the commercial release of genetically engineered (GE) crops include naturalization, introgression to sexually compatible relatives and the transfer of beneficial traits to native and weedy species through hybridization. To date there have been few documented reports of escape leading some researchers to question the environmental risks of biotech products. In this study we conducted a systematic roadside survey of canola (Brassica napus) populations growing outside of cultivation in North Dakota, USA, the dominant canola growing region in the U.S. We document the presence of two escaped, transgenic genotypes, as well as non-GE canola, and provide evidence of novel combinations of transgenic forms in the wild. Our results demonstrate that feral populations are large and widespread. Moreover, flowering times of escaped populations, as well as the fertile condition of the majority of collections suggest that these populations are established and persistent outside of cultivation.