**11.4 Background subtraction**

If the background is labeled using a non-specific antibody, the background signal can then be subtracted from the results of RIS (Sergides et al., 1999; Goldenberg et al., 1978). It should

Breast Cancer: Radioimmunoscintigraphy and Radioimmunotherapy 187

that target antigens located on the surface of the tumor cells such as anti-CEA antibodies, are eventually catabolized. Intracellular degradation of the targeting agent can be prevented by e.g. dextranation (Bue et al., 2000). Radiolabeling of antibodies with 90Y or 177Lu is performed by linking these radionuclides to chelators (DTPA or DOTA) which are chemical moieties that complex free metal ions. These chelators are conjugated to the antibodies and subsequently to the radiolabel. After catabolization of mAbs labeled with 90Y- or 177Lu-DTPA/-DOTA, the catabolic products are conjugated to, in most cases, lysine (e.g. 90Y- or 177Lu-DOTA-lysine). Whereas radioiodinated tyrosine is excreted by the cell, the 90Y- or 177Lu-DTPA/DOTA-lysine metabolites are trapped within the lysosomes, thereby increasing the tumor retention time of these radiolabels (Koppe et al., 2005). Cellular excretion can also be limited if the radionuclides are of metal type, e.g. indium or yttrium, and this is due to

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

1. Shorter circulating half-life and faster execration by kidney that leads to decrease

4. Reduce the HAMA response due to the loss of Fc fragment that is responsible for

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

The strength of the antibody:antigen interaction is measured through the binding affinity and is quantified through the association constant (Ka) (Boswell et al., 2007). Increasing Ka of antibody will be leads to an increase in uptake antibody in the tumor. However, they may be less able to penetrate deeply due to strongly bound at the tumor surface. The studies with iodine radiolabeled scFvs demonstrated that a threshold affinity between 10−7 and 10−8 M was required to observe detectable tumor uptake in mice 24 h post injection, whereas no gain in tumor accumulation was observed with affinities >10−9 M. Affinities >10−9 M were detrimental to rapid and uniform tumor penetration due to stable binding at the first pass of

Multivalency has been reported as an advantage in radioimmunotherapy (Dearling & pedley, 2007). Conversion of monovalent antibodies into multivalent format increases their functional affinity and decreases dissociation rates for cell-surface and optimizes biodistribution

2. Smaller molecular weight that leads to faster and more deeply diffuse into tumors. 3. Reduce non-specific antibody binding by Fc receptor on cells due to the loss of the Fc

intracellular retention of metal containing catabolic products (Press et al., 1996).

**11.10 Targeting agents** 

background signals.

fragment

**11.11 Antibody affinity** 

**11.12 Multivalency** 

of an antibody have several advantages including:

immune response to foreign proteins.

productions has high affinity for antigen (Sergides et al., 1999).

tumor antigens forming a binding site barrier (Adams et al., 2001).

be remembered that this technique leads to increase the total dose of radioactivity in the patient body that leads to undesirable side effects.
