Page 173 - Cellular Imaging in Regenerative Medicine, Cancer and Osteoarthritis

Summary, Discussion, Concluding remarks
to the pancreas. The radioactivity washout from the pancreas was relatively fast, while tumour radioactivity uptake declined at a lower rate. So, the optimal time window for the best tumour:pancreas ratio for pre-operative and intra-operative tumour detection would be around 24 h post injection. For translation to the clinic of the PA/SB3 combination, the stability of SB3 +/- PA in humans should first be tested before the concept can be introduced in patients.
The success of PRRT depends on the amount of radioactivity delivered to the tumour in relation to the dose delivered to healthy tissues. To improve or widen the use of PRRT, there is a wide field of research ongoing (41). Other, more powerful, radionuclides (e,g, α-emitters) could be used (42, 43), various kinds of combination therapies can be given (43-45), the administration routes of the radiopeptide can be adjusted (46, 47), or the DNA damage response can be enhanced (48, 49).
One of the tracers widely used for PRRT is DOTA-Tyr3-octreotate (DOTA- TATE) (50, 51). In the clinic we and many others apply radiolabelled DOTA- TATE to image and treat somatostatin receptor subtype 2 (SSTR2) positive, neuroendocrine tumours. For therapy [90Y]Y-DOTA-Tyr3-octreotide and [177Lu] Lu-DOTA-Tyr3-octreotate (51-53) are mostly used and the disease-control rates for these therapies are between 68–94% (54). The blood clearance of these tracers in humans is rapid (<10%ID in blood at 3 h post injection) (55). As there is no 100% response rate there is room to enhance the therapeutic efficacy. A higher dose in the tumor with the current tracer is not an option because concomitant higher radiation doses to other organs are also given. The organs at risk for long-term toxicity are predominantly the kidneys and the bone marrow. The renal radiation dose can however be reduced by co-infusion of a gelatin-based plasma expander (Gelofusine), leaving the bone marrow the main dose-limiting organ for treatment (56, 57). In Chapter 6 we described how we aimed to further improve the biodistribution of radiolabelled DOTA- TATE by prolonging the tracer circulation time by adding an albumin binding domain to the radiopeptide. This new tracer is called Albutate-1 and is expected to have a longer circulation time in the blood stream according to our concept, possibly resulting in more uptake by the SSTR2 positive cells. We determined the characteristics of [111In]In-albutate-1 and [177Lu]Lu-albutate-1
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