**7.1 Radionuclides for imaging**

178 12 Chapters on Nuclear Medicine

lesions, thus resulting in a relatively high false-positive rate in patient population. Several strategies have been developed over the past two decades for earlier and more accurate diagnosis of disease and to evaluate response to therapy. One of the novel approaches for specific detection of cancers is the use of monoclonal antibodies conjugated with radionuclides so-called radioimmunoscintigraphy (is also called radioimmunodetection, radioimmunoimaging and radioimmunodiagnosis) (Salouti, et al., 2006). In this method, a radio-isotope labeled antibody is administered to a patient with cancer. Once localized to the tumor tissue, the radioisotope (and hence the sites of malignancy) can be detected with a nuclear medicine imaging system like gamma camera. The summery of history for RIS has been shown in table 1. The efficacy of this technique depends on antigen expression on tumor cells compared to normal tissues. Affinity, specificity, pharmacokinethics, properties of the radionuclide and imaging technique have influence on the efficacy of radioimmunoscintigraphy. The potential clinical applications of RIS are (1) evaluation of patients with suspected breast cancer, (2) locoregional staging of newly discovered breast cancer, (3) detection of distant metastases using whole body scintigraphy and (4) evaluation of

tumor response to therapy (Berghammer et al., 2001).

parenterally into animals bearing tumors.

1953

1963

1965

1975

1983

in vivo.

effectively.

*in vivo*.

metastatic breast cancer.

<sup>1908</sup>Paul Ehrlich is generally recognised as the inventor of the term "magic bullets", describing the potential of an antibody to specifically target tumor cells.

<sup>1957</sup>Gamma camera as initially introduced in 1957 by Hal Anger was designed to detect gamma photons within an energy window between 30 and 300 keV.

This approach was invented by Pressman and his associates who discovered that radioiodinated antisera could concentrate selectively in tumors when injected

David Kuhl and Roy Edwards were the first to present tomographic images using the Anger camera by acquiring multiple planar images from different angles and back projecting data into a 3 dimensional space. The technology is called SPECT.

Gold and Freedman discovered carcinoembryonic antigen (CEA), the first well defined tumor-associated antigen and as a result of this finding purified

polyclonal anti-CEA antibodies were shown to localise to CEA expressing tumors

Discovery of the hybridoma technique by Kohler and Milstein was perhaps the

radioimmunoscintigraphy. Using the hybridoma technique, mass production antibodies of predetermined specificity with high quality became possible.

<sup>1978</sup>Goldenberg presented a trial using radiolabeled antibodies to detect breast cancer

fragments to improve the quality of nuclear medicine images of metastatic cancer

Methodologic improvements included the combined use of optimized radionuclide tracers such as SPECT and antibody fragments such as Fab

<sup>1986</sup>As a further advancement of chimeric mAbs, in 1986, Jones *et al*. reported the

<sup>1998</sup>Trastuzumab (Herceptin) was approved by FDA for using in patients with

<sup>2004</sup>Radioactive anti-HER-2/neu rhuMAb were considered attractive agents for radioimmunodiagnosis of aggressive HER-2/neu-positive breast carcinomas.

Table 1. The summery of history for radioimmunoscintigraphy.

single most important contribution to the development of

production of humanized monoclonal antibodies.

Ehrlich, 1906

Pressmanand Korngold, 1953

Anger et al., 1957

Kuhl & Edwards, 1963

Gold & Freedman, 1965

Kohler & Milstein, 1975

Goldenberg et al., 1978

Larson *et al.,*  1983a, b

Jones PT et al.1986

1999

Cobleigh et al,

Olafsen et al, 2004

The most common radionuclides in nuclear medicine are 99mTc, 123I, 67Ga and 111In. Lower energy γ-rays are readily absorbed in tissues and therefore less useful for external imaging. On the other hand, highest energy γ-rays cause to decrease the sensitivity of imaging system (Berghammeret al., 2001). Technetium-99m is so far the most commonly used radionuclide in nuclear medicine (Hamoudeh et al., 2008). This is due to the highly interesting physical properties of 99mTc which is advantageous for both effective imaging and patient safety perspectives. Its properties include short half-life (6 h), gamma energy at 140 keV with practically no alpha or beta emissions and latent chemical properties, facilitating thereby the labeling of several types of kits for versatile diagnostic applications and readily available and inexpensive (it is derived as a column elute from a 99Mo/99mTc generator) (Verhaar et al., 2000). It is most often used with smaller antibody forms such as Fab, scFv, diabodies and nanobodies. The gamma-ray emitting radionuclides are commonly used in gamma camera and single photon emission tomography (SPECT). Other groups of diagnostically used radionuclides are ß+ emitters such as 11C, 18F, 13N and 15O (Hamoudeh et al., 2008). The positron emitting radionuclides are used in positron emission tomography (PET). The positive electron travels only a short distance through the tissues and interacts with a free or loosely bound negative electron. The outcome of this interaction is two photons, consisting each of 511 keV energy and being given off in opposite directions (Boswell & Brechbiel, 2007).
