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A series of structurally modified Tm(3+) DOTAM-alkyl complexes as potential PARACEST MRI contrast agents has been synthesized with the aim to decrease the overall positive charge associated with these molecules and increase their biocompatibility. Two types of structural modification have been performed, an introduction of terminal carboxylate arms to the alkyl side chains and a conjugation of one of the alkyl side chains with aspartic acid. Detailed evaluation of the magnetic resonance imaging chemical exchange contrast associated with the structurally modified contrast agents has been performed. In contrast to the acutely toxic Tm(3+) DOTAM-alkyl complexes, the structurally modified compounds were found to be tolerated well during in vivo MRI studies in mice; however, only the aspartic acid modified chelates produced an amide proton-based PARACEST signal.

Several approaches towards asymmetrically derivatized peptide-decorated cyclens that yield lanthanide metal chelators, in which three of the nitrogen atoms of cyclen share a common substituent and the fourth nitrogen atom is differentially substituted, have been evaluated. The most effective route consisted of selective monoalkylation followed by peralkylation with a second different electrophile. The unique substituent also possessed a masked sulfanyl group that was suitable for subsequent chemoselective conjugation chemistry.

The authors elaborated their own modification of the separation and labelling of autologous thrombocytes by means of 111indium-oxine which can be implemented in Czechoslovak departments of nuclear medicine with standard equipment. A total of 123 separations and labellings were made and 85 administrations to patients. The effectiveness of labelling by the described method was 79.5 +/- 6.9%, the separation yield of thrombocytes with regard to complete blood 44.3 +/- 13.8%. The aggregating capacity of the labelled platelets assessed in vitro after ADP stimulation (adenosine diphosphate) was 39.5 +/- 10.1% difference in optic density of platelet rich and platelet poor plasma which is evidence of the preserved viability of thrombocytes. "Recovery" during the 120th minute after administration of normal suspensions was 62.2 +/- 17.9%, the survival time of labelled thrombocytes 8.2 +/- 0.74 days. In patients with idiopathic thrombocytopenic purpura the "recovery" was 49.4 +/- 18%, the survival period 2.9 +/- 1.8 days. In patients after transplantation of the kidney complicated by acute rejection there was an increased accumulation of labelled platelets in the area of the kidney (count rate index 2.32 +/- 0.45). In normally functioning transplanted kidneys the count rate index was 1.42 +/- 0.06. On their own material the authors demonstrate other possibilities of clinical application of scintigraphy by means of labelled autologous platelets (a method hitherto not described in the Ccezhoslovak literature) for the detection of intracardial and arterial thrombosis.