**6. Future prospects**

Several future implications have already been discussed above. One of the most important developments for bone seeking radiopharmaceuticals will be individualized medicine. The search for an optimized balance between efficacy and toxicity will be found rather in an individualized treatment plan than in new agents. Good predictors of efficacy and toxicity are needed for treatment monitoring. Several potential candidates were described above. They may be found in clinical evaluation, imaging and several laboratory parameters. A combination of these parameters may lead to a prediction model which may be used in daily practice.

Multimodality treatment has also been described above. Many combinations have potential. It has to be investigated which regimen will be most effective. Besides a direct anti-tumor effect which may be reached with chemotherapy (i.e. docetaxel), it is recognized that treatment directed to the bony environment may add to the overall efficacy of the treatment regimen. Bone seeking radiopharmaceuticals are bone-directed and may be of value in combination with other treatment modalities. Besides combinations with chemotherapy or bisphosphonates other interesting combinations may include for example atrasentan, or denosumab.

An important other issue is the timing of treatment with bone seeking radiopharmaceuticals. The frequency and interval of sequential treatment should be considered. Bone seeking radiopharmaceuticals are mostly used as a single shot treatment. When patients respond to the treatment repeated treatment is considered. In most instances this does not happen with a planned interval in mind but rather when symptoms reappear after an initial response. In fact this might be too late. It seems better to treat patients sequentially before symptoms reoccur. This was confirmed in a randomized controlled trial in prostate cancer patients treated with two dosages of 1.1 mCi 188Re-HEDP with an interval of eight weeks compared to single shot treatment. They did not only find an improved pain response with longer duration but surprisingly an improved survival as well (Palmedo et al. 2003). Safety of repeated treatment with bone seeking radiopharmaceuticals was also confirmed (Sartor et al. 2007). This enhancement of efficacy may be attributed to chronic inhibition of osseous metabolism preventing cancer cells to thrive in the bony environment. Most other oncologic compounds are used in a repeated fashion using several cycles to reach sufficient effect. It should be investigated which multiple treatment regimen is most suitable for bone seeking radiopharmaceuticals, and whether it is safe and more effective. It may be suggested that the best result in hormone-refractory will be reached using a multimodality treatment regimen with fractionation of all treatments to be effective over a prolonged period of time.
