1. Application of Radioisotopes 186Re and 188Re to Cancerous Tissue
For over 100 years, radiation therapy has been one of the most crucial aspects of
cancer treatment. Even though radiation is used as a palliative treatment, it still
eliminates a good portion of cancerous tissue. Usually about 4000-6000 rads (radiation
absorbed dose) are used in the target tissue because only a few tens of rads can be
tolerated.1 Rads are defined as 10-2 J/kg of absorbing material. Radiotherapy can affect
healthy tissue in the proximity of cancerous tissue and thus targeting of the radiation is
very important to minimize damage to the normal tissue. However, if cancer is not
treated metastases can occur. The fundamental goal in radiotherapy is to find a safe and
efficient way to treat cancerous tissue without affecting healthy tissue. Technetium (99m
depreotide) was originally produced from the synthetic substance Molybdenum-99 (Mo-
99) for radiodiagnostic purposes.
Tc-99m has a half-life of about six hours and emits 140keV gamma rays. This
Somatostatin derivative peptide was improved for radiotherapy of tumors with Rhenium.
It has been concluded that contrasting biodistribution (a method of tracking where
specific compounds travel in an experimental subject) studies between 99mTc and 188Re
showed a good relationship between the two metal complexes and demonstrated drawn-
out tumor confinement.2 Re-188 is useful for radiotherapy because of its seventeen-hour
half-life, 2.21 MeV beta emission, and 155 keV gamma emission. Re-188 has a longer
half-life than Tc-99m thus making it more available and useful in the field of
radiotherapy.
My responsibility in this project was to investigate a chelate system for Rhenium
(Re) that allowed conjugation to a targeting peptide for in vivo applications. We
investigated tetradentate chelate systems that contained four nitrogens (N4) as the donor
atoms to coordinate or bond to the Re in either the +5 or +3 oxidation state. The presence
of four donor atoms for the Re in the same chelate made it more stable in vivo. The
chelates we synthesized are shown below in Figure 1. The chelates used involved
reacting oxalaldehyde or malonaldehyde with 1H-indol-7-amine. This resulted in two
different sized chelates (the one with malonaldehyde is one CH2 (methylene) group larger.
We also investigated the possibility that one of these chelates could form the basis of a
bifunctional chelate, once derivatized, and be conjugated to a targeting peptide (such as
somatostatin analog).
One of the methods used was chelate synthesis. The method used was
synthesizing the following N4 chelates by a condensation reaction. One equivalent of the
appropriate aldehyde will be reacted with two equivalents of 1H-indol-7-amine to yield
the tetradentate N4 chelate. Two paths were used to reach the desired product. One
pathway is neat microwave-assisted synthesis on sodium bisulfate support.4 The other
route is removal of water by distillation. The N4 chelates then were isolated and
characterized by 1H-NMR (Nuclear Magnetic Resonance) and possibly 13C-NMRor mass
spectrometry.
Figure 1. Scheme showing the ligand syntheses.

2. The Re (V) complexes were characterized by reacting each of the two chelates with
ReOCl3 (PPh3)2 in boiling ethanol under a nitrogen atmosphere. Each of these would be
characterized by 1H-NMR, 13C-NMR, NMR, IR (Infrared Radiation), and MS (Mass
Spectrometry). We then synthesized the two N4 chelates according to literature
procedures.
References
1
Jurisson, Silvia S., andMary Jane Heeg. "The Role ofInorganic Chemistryin the Development ofRadiometal Agents forCancer
Therapy." American Chemical Society 32.12(1999): 1053-060.
2
John E. Cyr, Daniel A. Pearson,DavidM. Wilson, Carol A. Nelson, Mary Guaraldi, Michael T. Azure,JohnLister-James, Ludger
M. Dinkelborg, RichardT. Dean. “Somatostatin Receptor-BindingPeptides Suitable for Tumor Radiotherapy with Re-188 or Re-186.”
J. Med. Chem.; 2007; 50(6); 1354-1364.
3
IUPAC. Compendium of Chemical Terminology,2nded. (the "GoldBook").Compiledby A. D. McNaught andA. Wilkinson.
Blackwell Scientific Publications, Oxford(1997).XML on-linecorrectedversion: http://goldbook.iupac.org(2006-) createdby M.
Nic, J. Jirat, B. Kosata; updates compiledby A. Jenkins.ISBN 0-9678550-9-8.doi:10.1351/goldbook.
4
Microwave-assistedefficient synthesis of diimines in dry media usingsilica gel-supportedsodium hydrogensulfate as reusable solid
support. Bazgir, A. Journal of Chemical Research. 2006, 1,1-2.
O
O
H
N
NH2
NN
NH HN
N,N'-(ethane-1,2-diylidene)bis(indol-7-amine)
+ 2 + 2 H2O
1H-indol-7-amineoxalaldehyde
O
O
malonaldehyde
H
N
NH2
1H-indol-7-amine
NN
NH HN
N,N'-(propane-1,3-diylidene)bis(indol-7-amine)
+ 2 + 2 H2O