Diagnostic radiopharmaceuticals

In the last decade, a large number of radiolabeled small biomolecules have been studied for their potential as radiopharmaceuticals for diagnosis and radiotherapy of various diseases. This review wiU focus on some fundamental aspects of receptor-based diagnostic radiopharmaceuticals, including radiopharmaceutical design, receptors and receptor imaging, choice of biomolecule, and modification of pharmacokinetics. 

Table 3. Selected excimples of radiolabeled peptides as diagnostic radiopharmaceuticals ...

In the last chapter receptor-based diagnostic radiopharmaceuticals are reviewed including considerations on drug design, on receptors, and on receptor imaging with the objective of modifying the pharmacokinetics of these agents. 

These C(6)-radiohalogenated uracil derivatives 217-219 have been prepared282-284 as shown in equation 135 for evaluation as diagnostic radiopharmaceuticals. Direct irradia-... 

The surfactant protein B was unspecifically labelled with/ac-[99mTc(CO)3]+. The highly lipophilic protein spread over a hydrophilic surface and could have potential in the diagnosis of acute respiratory disease syndrome. The spreading properties of the labelled and native surfactant protein B were in coincidence, making labelled surfactant protein B a potential diagnostic radiopharmaceutical [122]. 

The type of decay of the radiopharmaceutical should also be adequate for its intended use. Diagnostic radiopharmaceuticals should decay by y emission, electron capture, or positron emission, and never emit a or even [I particles. On the contrary, therapeutic radiopharmaceuticals should decay by a or p emission because the intended effect is in fact radiation damage to specific cells. 

Regarding the energy emission of diagnostic radiopharmaceuticals, the finally produced y rays should be powerful enough to be detected from outside of the body of the patient. The ideal energy for nuclear medicine equipment is around 150 keV. y rays should be monochromatic and photon abundance should be high to decrease the imaging time. 

Ready-for-use diagnostic radiopharmaceuticals which are intended for transport over some distance typically include radionuclides with half-lives from 13 h and up. 

Liu S, Edwards DS. 99mTc-Labeled small peptides as diagnostic radiopharmaceuticals. Chem. Rev. 1999 99 2235-2268. 

Small-volume injectables can be therapeutic injections, ophthalmics, diagnostics, radiopharmaceuticals, or allergenic extracts. The active ingredients can be intended for human or animal therapy and can be small molecules, proteins and other large molecules, biologies, vaccines, monoclonal antibodies, antisense oligonucleotides, and, in the future, genes. 

In addition to studies of classic bone seeking pharmaceuticals with a therapeutic potential, an evaluation was made of the receptor ligand peptide TATE to determine its potential as a diagnostic radiopharmaceutical (chelated by HYNIC and labelled with T) and as a therapeutic one (chelated by DOTA and labelled with therapeutic radioisotopes ( °Y and Lu) and a diagnostic isotope ( 4n)). 

O. H. Kapp, J. Siemion, W. C. Eckelman, V. I. Cohen, R. C. Reba. Molecular modeling of the interaction of diagnostic radiopharmaceuticals with receptor proteins m2 antagonist binding to the muscarinic m2 subtype receptor. Recept Signal Transduct. 1997, 7, 177-201. 

Liu GZ, He J, Dou SP et al (2004) Pretargeting in tumored mice with radiolabeled morpholino oligomer showing low kidney uptake. Eur J Nucl Med Mol Imaging 31 417-424 Liu S, Edwards DS (1999) Tc-99m-labelled small peptides as diagnostic radiopharmaceuticals. Chem Rev 99 2235-2268... 

Ponto JA, Swanson DP, Freitas JE (1987) Clinical manifestations of radio-pharmaceutical formulation problems. Hladik WB 111, Saha GB, Study KT (eds) In Essentials of nuclear medicine science. Williams Wilkins, Baltimore, pp 268-289 Saha GB (1987) Normal biodistribution of diagnostic radiopharmaceuticals. In Hladik WB III, Saha GB, Study KT (eds) Essentials of nuclear medicine science. Williams Wilkins, Baltimore, pp 6-7... 

Saha GB (1987) Normal biodistribution of diagnostic radiopharmaceuticals. In Hladik WB III, Saha GB, Study KT (eds) Essentials of nuclear medicine science. Williams Wilkins, Baltimore, pp 3-19... 

The object of this review is to introduce inorganic chemists to the subject of radiopharmaceuticals. Radiopharmaceuticals are compounds containing radioactive nuclides which are useful in the diagnosis or treatment of certain disease states. Since most research is presently focused on diagnosis, the chemical aspects of diagnostic radiopharmaceuticals will be treated here. In addition, radiopharmaceuticals can be used either iji vitro or in vivo and only the latter type will be discussed. 

This is occurring in parallel with large increases in demand for short-lived diagnostic radiopharmaceuticals for cancer detection and staging, especially cyclotron produced FDG (fluorodeoxyglucose). While the number of small cyclotrons to supply is increasing rapidly... 

A more recent work on the development of a BFC for Ga " is based on a S3N tetra-coordinate chelator (O Fig. 45.8) (Luyt and Katzenellenbogen 2002). It shows high stability at neutral aqueous conditions when coupled to an amino acid mimicking a peptidic vector molecule. This could be interesting for the use with gallium labeled diagnostic radiopharmaceuticals. 

The most important pharmaceutical radionuclide produced by a nuclear reactor is molybdenum. This element is the mother radionuclide in a Mo/ " Tc-generator (see Sect. 15.6.4). During separation in this generator sodium "technetium pertechnetate is formed. Tc-pertechnetate is the most frequently used radiochemical for coupling to a pharmaceutical ligand in the preparation of diagnostic radiopharmaceuticals. 

For all investigational medicinal products (IMPs) used in a clinical trial EU Directive 2001/20/EC ( CUnical Trial Directive ) and GMP Annex 13 are applicable [6, 7], see Sect. 35.5.10. The clinical trial directive has recently been replaced by the new and less stringent EU regulation 536/2014 [8,9]. In this regulation, GMP and a manufacturing license will no longer be required for the preparation of diagnostic radiopharmaceuticals used in clinical trials when they are prepared in a hospital radiophaimacy from licensed sources and used within the Member State. 

Diagnostic radiopharmaceuticals are given in extreme low doses in order to minimise radiation exposure. This can be... 

TMew clinical trial regulation is less stringent for diagnostic radiopharmaceuticals [9]... 

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