Radionuclides biomolecules

Fig. 10. Typical chelating agents for radionuclides having the ability for further derivatization with biomolecules for targeted delivery.

Fig. 3. Distribution and elimination of a radiopharmaceutical following administration (M-BFC-BM M=radionuclide M = metal ion in the blood stream BFC = bifunctional chelator BM = biomolecule L = competing chelator)...

Some selected metallic radionuclides useful for radiotherapy are shown in Table 1. In general, identifying the most appropriate isotope for radiotherapy is often a difficult task and requires balancing a variety of factors. These include tumor uptake and retention of the radiolabeled BFC-biomolecule (BM)... 

Fig-1 Schematic presentation of the radiopharmaceutical design. The targeting biomolecule serves as the vehicle to carry a radionuclide to the receptor site on tumor cells. The radionuclide is the radiation source. The bifunctional chelator (BFC) is used for radiometal chelation and attachment of the targeting molecule. The linker is often used for modification of pharmacokinetics. Diethylenetriaminepentaacetic acid (DTPA), 1,4,7,10-tetraaza-cyclododecane-N>N, N">Ar,"-tetraacetic acid (DOTA)... 

Development of therapeutic radiopharmaceuticals is one of the areas most widely explored by researchers. The many significant advances in this field have solved many of the technical problems involved in labelling biomolecules with a variety of radionuclides. These studies have the potential to provide a large array of target specific therapeutic radiopharmaceuticals [1.17]. However, to assist in the identification of an ideal agent, rehable laboratory methods for screening the potential candidates are essential. 

From 1998 to 2001, the IAEA conducted a CRP on techniques for labelling biomolecules for targeted therapy, whose participants developed several protocols and standard operating procedures for labelhng peptides with metallic radionuclides and iodine isotopes. These results are published in Ref. [1.21]. For the current CRP, it was decided to adopt the relevant results reported in that pubhcation. 

Radioiodination is one of the simplest ways to radiolabel a biomolecule. Several radionuclides of iodine are available for SPECT or PET I Tables 6.7-1... 

As Cu has many interesting radionuclides for therapeutic as well as for diagnostic applications (O Tables 45. i and O 45.2), the development of ideal chelators for this metal is of interest. BFCs used for the coupling of Cu-radioisotopes to biomolecules are based on the 14-membered tetraazamacrocycle cyclam 14 (1,4,8,11-tetraazacyclotetradecane) O Fig. 45.17). Two bifunctional versions of cyclam-14, 4-[(l,4,8,ll-tetraazacyclotetradec-l-yl)methyl]-benzoic acid (= CPTA) and [6-(p-bromoacetamido)benzyl]-l,4,8,ll-tetraazacyclotetradecane-l,4,8,ll-tetraacetic acid (= BAT) (O Fig. 45.17), were coupled to monoclonal antibodies and somatostatin analogs (Smith-Jones et al. 1991 Anderson et al. 1995 Wilder et al. 1996). In addition to... 

Applications of radionuclides to biological vectors and their use in vivo demands that the radiometal (metallic radionuclide) remains strongly associated with the targeting biomolecule. 

The chemistry of iodine radionuclides used in nuclear medicine has been extensively explored. Isotopic exchange procedures, direct iodination approaches (those using chloramine-T and iodogen), and indirect approaches (the Bolton-Hunter method) are but a few of the well-known synthetic strategies to label biomolecules with iodine (24). Some of the most important 1-labeled imaging tracers [1-labeled iodoazomycin arabinoside ( lAZA), 1-labeled vasoactive intestinal peptide ( 1-VlP), etc.] will be discussed in the following sections. 

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