**11.10 Targeting agents**

186 12 Chapters on Nuclear Medicine

be remembered that this technique leads to increase the total dose of radioactivity in the

In the latter application, RIS is performed as a scouting procedure prior to RIT to enable the confirmation of tumor targeting and the estimation of radiation dose delivered to both tumors and normal tissues. For this purpose, the radioimmunoconjugates used for RIS and RIT should demonstrate a similar biodistribution and therefore radionuclides with comparable chemical properties have to be chosen (Dearling & pedley, 2007). When using 131I for RIT, both 123I and 131I can be used for a RIS scouting procedure. When using 90Y for RIT, 111In can be used to represent this pure beta-emitter (Dearling & pedley, 2007). Finally, when aiming the therapeutic use of 186Re or 188Re, either these radionuclides

The result of experiments indicated that increasing the dose of antibody will increase the amount of radioactivity in the tumor (Begent et al., 1987). On the other hand, this technique has side effects due to HAMA response against the dramatic rise in dose of administered

The resolution of latest-generation of PET and SPECT cameras has been improved and the combination of these systems with an integrated CT (and also MRI) has led to a much better interpretation of the data (Dearling & pedley, 2007). In addition, the indirect combination of nuclear imaging and optical imaging systems can also serve shared purposes (Munnink et

The background counts can be reduced by removing radioactivity from the circulation. This can be achieved by the use of a second antibody active against the RIS antibody. In this technique, after the binding time of original antibody to tumor tissue, the second antibody administers to the patient (Sergides et al., 1999). The second antibody binds to the radioactive antibody that remains in the blood stream. The reticuloendothelial system uptakes antibody-antibody complex and leads to concentrate radioactivity in liver and spleen. This technique leads to increase in T/B ratio without adverse effects. The only disadvantage of this method is limitation in the detection of metastases at liver and spleen

One significant factor that influences the absorbed radiation dose to the tumor is the fate of the radiolabel after internalization of the radiolabeled mAb into the tumor cells. In case of internalisation, the radionuclides will come closer to the critical radiation target, i.e. nuclear DNA. Internalization of the antibody depends on various factors including the antibody, the targeted antigen and the tumor cells. On the other hand, internalisation might be disadvantageous, if it leads to quick degradation of the targeting agent followed by diffusion and elimination of the radionuclide (Boswell et al., 2007). Most antibodies including those

themselves can be used for an imaging procedure or 99mTc (Pontus et al., 2004).

antibody that limits the application of this technique (Dearling & pedley, 2007).

**11.9 Improving the internalization of the radiolabeled mAb** 

patient body that leads to undesirable side effects.

**11.5 Pre-scouting** 

**11.6 Increasing the dose delivery** 

**11.7 Combined imaging systems** 

al, 2009).

**11.8 Second antibody** 

(Sergides et al., 1999).

RIS may be improved by the production of superior targeting agents to deliver radioactivity to tumor sites. For example, instead of using intact antibodies to target tumors, fragments of antibodies retaining their antigenic specificity can be used (Sergides et al., 1999). Fragments of an antibody have several advantages including:


Further improvements in the structure of antibodies are being explored with antibody engineering technology. Single-chain antigen binding fragments (sF7) consisting of variable heavy (VH) or variable light (VL) domains and recombinant sF7 peptides which are VH and VL domains connected by peptide linkers are the productions of this technology. These productions has high affinity for antigen (Sergides et al., 1999).
