The technical progress of recent years has been made possible by advancing computational resources leading to improved planning and application technologies and by congenial engineering developments like multi-leaf collimators and on-site positioning control. However, all these developments would not have been possible without medical imaging (Fig. 4.1). By the 1980s, CT was integrated into radiotherapy planning [1]. While the first intentions were rather aimed at better geometrical and physical treatment planning (until today, CT tissue density data are used for the calculation of beam attenuation within the patient), it became obvious very soon that the (patho)anatomical informations could also be used for target definition and normal tissue identification. This has triggered the development of modern target volume concepts and planning techniques. Today, we have highly precise technologies of treatment planning an delivery available, e.g., intensity-modulated radiation therapy (IMRT) and stereotactic radiotherapy (SRT, SBRT), which enable safe high-dose treatment of precisely defined target volumes with simultaneous sparing of normal tissues [2]. IMRT techniques enable the radiation oncologist to spare organs like the spinal cord or the parotid glands while giving therapeutic radiation doses to neighboring tumors, e.g., in the head and neck area [3]. It is possible to spare the rectum and the bladder while giving high-dose curative treatment to prostate cancer [4] and to cure benign tumors of the base of the skull with a minimum of neurological late sequelae [5]. Stereotactic radiotherapy of brain metastases preserves the quality of life of many of cancer patients without neuropsychological toxicity [6, 7], while stereotactic radiotherapy of localized lung cancers in inoperable patients has improved the prognosis of this patient group on an epidemiologically measurable scale [8].

Modern IMRT techniques have also opened the door to the application of various dose levels within one treatment. Practical implementations are simultaneously integrated boost techniques, where, e.g., the macroscopic tumor and the areas of assumed microscopic spread are covered by high- and intermediate-dose ranges (Fig. 4.2) [9]. Beyond this, the so-called dose painting has become possible, where radiotherapy adaptation within a given target can be defined by biological properties of certain sub-volumes. Using IMRT, e.g., hypoxic regions within a tumor assumed to be radioresistant, might be treated with dose prescriptions on the basis of hypoxia-PET imaging [10]. This is a very interesting field for the use of molecular imaging techniques for radiotherapy. First studies in the head and neck tumors presently address this option [11]; however, clinical outcome data have to be awaited before introducing these techniques into clinical practice.

The new particle beam technologies like proton and heavy ion therapies promise even better dose distributions. Due to their physical properties, the treatment dose can be delivered to a very confined area with perfect sparing especially of the normal tissues behind the target. However, being very sensitive to the physical properties of the tissue, these methods also rely on imaging as a prerequisite for successful treatment planning and delivery [12].

Re-irradiation has been largely avoided in the past, due to the risk of severe normal tissue toxicity. But with a more precise definition and 3D dose documentation together with growing clinical and radiobiological knowledge, re-irradiation can now also be given more frequently, provided that restaging reveals localized tumor progression and the area of progression can be defined clearly (Fig. 4.3) [13–17].

Overall, in the light of all these new possibilities, accurate staging and depiction of the geometry of malignant spread are a prerequisite for effective and precise radiotherapy applications. While very high doses are given inside of target volumes, a rather low exposure is often achieved in their direct neighborhood (Fig. 4.4). Technical and interpretational imaging errors may directly translate to impaired local tumor control and/or increased risk for normal tissue toxicity. Furthermore, erroneous interpretation of posttreatment changes may lead to unnecessary interventions and patient discomfort.

This chapter will go through the relevant applications of imaging in radiotherapy and aims at increasing the awareness of the reader about radiotherapy specific questions and requirements for molecular imaging.