This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide ¹²⁵I, and the stable isotope ¹⁰B, which becomes radioactive upon neutron activation. ¹²⁵I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated ¹⁰B emits highly cell killing α-particles and ⁷Li³⁺ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising.

The thesis can be divided into three parts:

i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of ¹²⁵I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield.

ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam.

iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with ¹²⁵I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented.

The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by ¹²⁵I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.

This thesis describes the synthesis and radiohalogenation of compounds of potential use for tumor targeting.

The first section describes the synthesis and radioiodination of DNA intercalating compounds. The compounds are derivatives of 9-aminoacridine, and the anthracyclins daunorubicin and doxorubicin. The precursor compounds were labeled with ¹²⁵I (T_1/2 = 60 days), which is an Auger emitting nuclide. ¹²⁵I decaying in the close vicinity of DNA is known to have a much higher cell killing effect than ¹²⁵I decaying in the cytoplasm and some of the labeled compounds prepared in this thesis are currently being tested for use in targeted radionuclide therapy for cancer.

The second section describes the radiobromination of closo-carboranes by subjecting the corresponding iodinated compounds to palladium-catalyzed halogen exchange using [⁷⁶Br]bromide. The ⁷⁶Br isotope (T_1/2 = 16.2 h) is a positron emitting nuclide that is suitable for PET studies. Via the halogen exchange reaction good to excellent radiochemical yields of radiobrominated closo-carboranes were obtained. The results of the present study may prove to be applicable to pharmacokinetic studies of carboranes and their derivatives.

The third and final section describes the indirect radiobromination of the trastuzumab anti-HER2 monoclonal antibody and of the anti-HER2 Affibody by means of an “one-pot” procedure using N-succinimidyl-5-(tributylstannyl)-3-pyridinecarboxylate (SPC) and ((4-hydroxyphenyl)ethyl))maleimide (HPEM), respectively. It was found that SPC and HPEM can be efficiently radiobrominated and thereafter coupled to the antibody and Affibody, respectively. The labeled proteins retained their capacity to bind specifically to HER2 expressing SKOV-3 cells in vitro. Application of this method to ⁷⁶Br might enable the use of PET in the detection of HER2 expression in breast, ovarian, and urinary bladder carcinomas.