DEPARTMENT OF RADIOPHARMACEUTICALS

DEVELOPMENT


STUDY PREPARATION OF 166 Ho LABELLED COMPOUNDS FOR THE ENDORADIOTHERAPY AND SKIN CANCER THERAPY


 


The study focused on the possibility of preparation of 166Ho-chitosan complex, 166Ho-poly(L-lactic acid) microspheres (PLA-MS), 166Ho-macroaggregates (MA) and 166Ho foils. The 166Ho radioisotope was prepared in Nuclear Research Institute plc at Řež, using the 165Ho(n,?)166Ho reaction, at the LVR-15 reactor (10 MW) with the neutron flux density 1014 cm-2.s-1.
The chitosan (poly-D-glucosamine, abbreviated as CHICO), is a natural biodegradable polymer 2-3. By means of its free amine groups, it forms a chelate-type complex with elemental Ho. The CHICO-complex radiation stability dependence on the pH of the reaction mixture and the specific activity of 166Ho was studied. In order to produce 3.7 GBq/mg 166Ho, holmium nitrate was irradiated for 10 hours. Also, the dependence of the CHICO labelling yield on the pH and CHICO/Ho concentration ratio were studied (Tab.1.).
 

Table 1. Effect of pH on complexation 166Ho-chitosan - starting 166Ho activity : 229.4 MBq/ml (6.2 mCi/ml)
pH solution
166Ho/166Ho-Chito (%)a)
Rf complex
2.08
89.9
0.05
2.92
90.7
0.02
3.38
91.2
0.00
4.04
89.5
0.02
5.10
85.6
0.02
Holmium  concentration  0.94 mg/ml, 1% chitosan in  1% acetyl acid
a) ITLC method -SA, MeOH(49):H2O (49): acetic acid (2)

The radiochemical purity of the prepared 166Ho-CHICO complex was determined by the radio-TLC method (Gelman-SG, mobile phase methanol, water and acetic acid mixture [49:49:2% Vol.]). The yield of the CHICO labelling (95 %) was found to be independent on pH within the range from 2.08 to 4.07, then it is slowly decreasing at pH=5. The 166Ho specific activity does not influence the yield of the CHICO labelling (Tab.2.)

Table 2. Effect of holmium concentration on yield complexation 166Ho-chitosan

[Ho] mg/ml
L/Hoa)
166Ho/166Ho-Chito (%)b)
Rf complex
0.94
10.94:1
89.3
0.02
1.87
5.47:1
89.9
0.05
2.80
3.66:1
88.3
0.05
3.74
2.77:1
90.3
0.02
7.48
1.37:1
88.1
0.02
a) L formal items of the ligand
b) ITLC method -SA, MeOH(49):H2O (49): acetic acid (2)

As a next step, several Ho-PLA-MS and Ho-MA inactive samples were prepared. Samples were subjected to sonication and the particle size distribution was checked using the electron microscope. Ho-PLA-MS and Ho-MA were then irradiated for 6 hours to produce 394.8 MBq/mg and 1265 MBq/mg, respectively. After the irradiation, the in-vitro stability of the complexes was studied,
Finally, several aluminum foils (of 10 x 10 mm dimension), covered by 165Ho and intended for skin cancer therapy, were prepared and irradiated for 10 hours to produce 800-1000 MBq 166Ho. After the irradiation, the 166Ho homogeneity distribution was analyzed using autoradiographic method.



More information?:  melichar@ujf.cas.cz

Department of Radiopharmaceuticals