Preclinical Evaluation of Radiolabeled DOTA-Derivatized Cyclic Minigastrin Analogs for Targeting Cholecystokinin Receptor Expressing Malignancies

Targeting of cholecystokinin receptor expressing malignancies such as medullary thyroid carcinoma is currently limited by low in vivo stability of radioligands. To increase the stability, we have developed and preclinically evaluated two cyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-minigastrin analogs radiolabeled with (111)In and (68)Ga.

Three-dimensional primary stability of cementless femoral stems

OBJECTIVE: This study investigates by means of a new bone-prosthesis interface motion detector whether conceptual design differences of femoral stems are reflected in their primary stability pattern. DESIGN: An in vitro experiment using a biaxial materials testing machine in combination with three-dimensional motion measurement devices was performed. BACKGROUND: Primary stability of uncemented total hip replacements is considered to be a prerequisite for the quality of bony ongrowth to the femoral stem. Dynamic motion as a response to loading as well as total motion of the prosthesis have to be considered under quasi-physiological cyclic loading conditions. METHODS: Seven paired fresh cadaveric femora were used for the testing of two types of uncemented femoral stems with different anchoring concepts: CLS stem (Spotorno) and Cone Prosthesis (Wagner). Under sinusoidal cyclic loading mimicking in vivo hip joint forces a new measurement technique was applied allowing for the analysis of the three-dimensional interface motion. RESULTS: Considerable differences between the two prostheses could be detected both in their dynamic motion and total motion behaviour. Whereas the CLS stem, due to the wedge-shaped concept, provides smaller total motions, the longitudinal ribs of the Cone prostheses result in a substantially smaller dynamic motion. CONCLUSIONS: The measuring technique provided reliable and accurate data illustrating the three-dimensional interface motion of uncemented femoral stems.

[DOTA]Somatostatin-14 analogs and their (111)In-radioligands: effects of decreasing ring-size on sst1-5 profile, stability and tumor targeting.

Multiple somatostatin receptor (sst)-subtype expression has been manifested in several human tumors. Hence, the availability of radiopeptides retaining the full pansomatostatin profile of the native hormone (SS14) is expected to increase the sensitivity and broaden the clinical indications of currently applied sst2-preferring cyclic octapeptide radioligands, like OctreoScan(®) ([(111)In-DTPA]octreotide). On the other hand, SS14 has been excluded from clinical use due to its rapid in vivo degradation. We herein present a small library of seven novel cyclic SS14-mimics carrying at their N-terminus the universal chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for stable binding of medically useful radiometals, like (111)In. By decreasing the number of amino acids composing the ring in their structure from 12 up to 6 AA, we induced important changes in key-biological parameters in vitro and in vivo. In particular, we observed unexpected changes and even total loss of sst1-5-affinity (6AA-ring), as well as weaker sst2-internalization efficacy as the ring size decreased. In contrast, in vivo stability increased with decreasing ring size, reaching its maximum in the 6AA-ring analogs. Interestingly, only the 12AA- and 9AA-ring members of this series showed sst2-specific uptake in AR4-2J tumors in mice revealing the prominent role of ring size on the biological response of tested SS14-derived radioligands.