Translation of New Molecular Imaging Approaches to the Clinical Setting: Bridging the Gap to Implementation

Abstract

Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential meaningful role for the tracer in the clinical setting-such as in staging, in the (early) prediction of a treatment response, or in supporting drug choices. So far, only 18 F-FDG PET has been incorporated into breast cancer guidelines. For proof of the clinical relevance of tracers, especially for analysis in a multicenter setting, standardization of the technology and access to the novel PET tracer are required. However, resources for PET implementation research are limited. Therefore, next to randomized studies, novel approaches are required for proving the clinical value of PET tracers with the smallest possible number of patients. The aim of this review is to describe the process of the development of PET tracers and the level of evidence needed for the use of these tracers in breast cancer. Several breast cancer trials have been performed with the PET tracers 18 F-FDG, 3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT), and 18 F-fluoroestradiol ( 18 F-FES). We studied them to learn lessons for the implementation of novel tracers. After defining the gap between a good rationale for a tracer and implementation in the clinical setting, we propose solutions to fill the gap to try to bring more PET tracers to daily clinical practice. Mol ecular imaging with PET is a rapidly emerging approach in oncology. This approach offers the potential to noninvasively determine tumor staging, make tumor response measurements, and characterize relevant drug targets in the tumor. Moreover, the wholebody 3-dimensional image provides information about all tumor lesions within a patient. This information is increasingly of potential interest because of progressive awareness of the existence of tumor heterogeneity for several clinical relevant characteristics (1,2). Interestingly, the development of tracers for most hallmarks of cancer allows the imaging of key characteristics of tumors in the research setting (3). More than 30 different PET tracers have been analyzed for their contributions to staging or early response measurements in breast cancer (Table 1). In addition, in the past 5 y, information on 15 different breast cancer tracers has been published. Many more are expected. However, at present, only the visualization of glucose uptake with 18 F-FDG PET is part of standard care and has been incorporated into breast cancer guidelines (4,5). New initiatives are attempting to bridge the gap between new chemical entities and clinical-grade radiopharmaceuticals, which then must be brought to the clinical setting. This process requires proof-of-concept feasibility studies; when sufficient evidence has accumulated, the tracer should be implemented in the clinical setting.The aims of this review are to summarize the steps from preclinical to ...

Imaging Cobalamin Uptake within Malignant Breast Tumors In Vivo

“…The instrumentation of MBI, which includes positron emission mammography (PEM), single-photon mammography (SPM), and positron emission tomography/X-ray computed tomography (PET/CT), and the employment of these modalities in imaging the uptake of various metabolic tracers within breast tumors was recently reviewed [5,6].…”

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

“…PET imaging is utilised to obtain information on the noninvasive observation of chemical processes in tissues/organs. The radiotracer locates and binds to the receptor of interest and it is important that the imaging agent does not lead to significant receptor occupation [298].…”

In vitro cytotoxic and genotoxic evaluation of peptides used in nuclear medicine (DOTATATE and Ubiquicidin29-41) in CHO-K1 cells

“…The success of treatment or diagnosis depends fundamentally upon the choice of an appropriate radionuclide and its carrier molecule, in order to ensure that the radionuclide is delivered directly to the tumor target. Several associations between carriers and isotopes are currently marketed, comprising a family of products for use in human health that shows diagnostic and therapeutic potential (Chaturvedi and Mishra 2016;van Es et al 2016).…”