Overview of the work plan

The CRP work plan was proposed at the project s first Research Coordination Meeting (RCM), held in Bucharest in October 2002. The evaluation of a new therapeutic radiopharmaceutical depends on several analytical techniques to establish the product s stability and chemical, radiochemical and pharmaceutical purity. In addition, specific bioassays must be developed to evaluate its biological efficacy. These bioassays are product specific and thus need to be worked out separately for each radiopharmaceutical. Participants also identified potential lead molecules and isotopes to be used during the CRP for the development of therapeutic radiopharmaceuticals. 

The following sections describe the major components involved in the development of therapeutic radiopharmaceuticals and the activities undertaken during the CRP aimed at developing comparative evaluation methods. 

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. 

The degree of receptor mediated uptake was determined by biodistribution studies of the radioconjugate in normal mice. At a minimum, biodistribution studies were to be done at 1,4 and 24 h post-injection for evaluation of the products. However, for accurate dosimetry calculations, biodistribution studies were to be performed at up to seven time points post-injection. 

Three methods were considered to be suitable for the assessment of cytotoxicity MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay, micronucleus assay and analysis by flow cytometry. The rationale for this sequence is outlined in detail in Appendix I. 

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