CHAPTER 2 2. LITERATURE SURVEY 2.1. Brief History of Germanium (Ge) 2.1.1. Natural Occurrence Germanium (Ge) is a semiconductor metalloid which belongs to group IV-A of periodic table. Ge is always found in combination with other elements such as argyrodite (a sulfide of Ge and Ag), Germanite (containing 8% of element), in Zn ores and other minerals. A significant concentration (≈ 2-8 ppm) of Ge also occurs in coals worldwide. It is recovered as a byproduct of production of some metals mainly Zn, Pb and Cu [1-3]. 2.1.2. Discovery of Germanium It was firstly predicted by D. I. Mendeleev in 1871 in his table of elements . This unknown element was called eka-silicon . In the year 1886, a German chemist Clemens Winkler was succeeded to produce elemental Ge from isolated argyrodite (Ag8GeS6) by reduction of sulfide . The physical and chemical properties of the Ge were in very good agreement with the ones predicted by Mendeleev in 1871 . 2.2. Physical and chemical properties of Germanium Germanium has greyish white appearance with submetallic luster and is very brittle element. Its atomic number is 32 and relative atomic mass is 72.61. It’s melting and boiling points are 1210.6 K and 3103.2 K respectively . 2.3. Importance of Germanium Germanium has refractive index of 4.0 and a Mohs hardness of 6.0. Any infrared bulk transmitting material with low dispersion properties and highest refractive index across a wide range of temperatures keeps off chromatic deviation in many applications. This means, the imaging using single Ge lens with low f-number can be achievable using the combination of low dispersion and high refractive index. The mechanical ruggedness and surface hardness of Ge is also helpful in many applications . A number of applications of Ge can be found in the field of nuclear physics such as highresolution gamma-ray detectors, low temperature thermistors and for IR detectors [4, 9]. Table 2.1 Chemical and physical properties of Ge  Properties Eka-Silicium  Germanium  Present values  72 73.32 72.61 Dark grey Greyish white Greyish white 5.5 5.47 5.323 High - 1246.2 13 13.22 13.57 0.306 0.318 0.310 4 4 4&2 Eka-SiO2 GeO2 GeO2 4.7 4.703 4.228 Reacts acidic Confirmed Confirmed Eka-SiCl4 GeCl4 GeCl4 1.9 1.887 1.8443 333-373 359 356.3 Soluble in (NH4) Confirmed Confirmed Eka-SiEt4 GeEt4 GeEt4 Density [gcm-3] 0.96 0.99 0.991 Boiling point [K] 433 436 435.7 Relative atomic maa Color Density [gcm-3] Melting point [K] Atom volume [cm3] Specific heat [Jg-1K-1] Valency Oxide Formula Density [gcm-3] Properties Chloride Formula Density [gcm-3] Boiling point [K] Sulfide Properties HS/H2O Ethyl derivative Formula 2.4. Isotopes of Germanium There are nineteen known radioisotopes of Ge. Among these seven radioisotopes (64Ge – 71Ge with a stable 70Ge) are proton rich and decay with β+ and/or electron capture. Nine isotopes (75Ge – 84Ge with a stable 76Ge) decay with β- and these are neutron rich. There are only four metastable isotopes of Germanium (71mGe, 75mGe, 77mGe and 79mGe) which are very lived. The longest-lived radioisotope is 68Ge with decay characteristics of 270.8 ± 0.3 days [3, 12-15]. 2.5. Medical applications and importance of 69Ge Germanium-69 (t1/2 = 39.05 h) is a PET trace Cyclotron produced radionuclide . It is a peculiar positron emitting (21% β+, Emax = 1205 keV) radionuclide . In the field of nuclear medicine, due to its favorable decay characteristics, it is an ideal choice to use 69 Ge-labelled antibodies for immuno-PET imaging . Also, it is cost effective and has simple and good production route [16, 17]. However, its full potential is yet to be examined for Positron Emission Tomography (PET) . The major limitations in the use of 69 Ge are the unavailability of appropriate radiolabeling techniques and its complex coordination chemistry for the synthesis of 69 Ge-based radiopharmaceuticals . Using fast and highly particular chelator-free strategy, the above said challenge can be circumvented by incorporation of 69 69 Ge onto SPION [18, 19] which can be used to establish Ge-SPION@PEG  that may prove a promising agent simultaneous for PET/MR imaging in future . Furthermore, it can also be beneficial for clinical diagnosing and staging of cancer disease . The presence of carboxyl group and some other specific ligands (proteins, antibodies or peptides)  at the surface of 69 Ge-SPION@PEG which may make it more powerful theragnostic agent for cancer. The chelator-free approach can also be used to prepare multifunctional theragnostic agents both for therapy and integrated imaging by incorporation of relevant therapeutic isotope such as 77 Ge (t1/2 = 11.3 h, Emax = 2.2 MeV, 100% β-) . Table 2.2 Nuclear data for 69Ge radionuclide Atomic number t1/2 Decay mode (ratio) Eβ MeV Iβ % Ref. 32 39.05 h β+/EC 1.215 32 [22-25] (23/77) 0.61 3.6  0.22 0.7 Figure 2.1 a) After the i. v. injection into mice the serial in vivo images of 69 Ge-SPION@PEG (top) and free 69Ge (bottom) . b) Before and after i. v. of 69Ge-SPION@PEG in vivo MR images of mice. Trans axial images are presented to show accumulation, contrast enhancement and up taking of 69 Ge-SPION@PEG in the kidneys . 69 Figure 2.2 a) In vivo imaging of lymph nodes with PET after hypodermic injection of Ge-SPION@PEG into the left footpad of the mouse. Lymph nodes and paws are indicated respectively by green and red arrows . b) Quantification of the 69Ge-SPION@PEG up taken by the paws and nodes of mouse . c) Before and after in vivo lymph node mapping with MRI after injecting of 69 Ge-SPION@PEG into the left footpad of the mouse . Darkening of lymph node is clearly visible (dashed green circles), whereas for the contralateral lymph node, there is no enrichment has observed (dashed red circles). 2.6. Production routes of 69Ge There are 19 production routes of 69Ge in EXFOR “retrieve listing only”. Among these routes only five charged particle induced reactions are chosen for the current study. Those reactions in which Ge was taken as target are excluded because they may have isotropic impurity. Moreover, those reactions are also excluded in which heavy projectiles are used. 2.6.1. Production Routes 59 Co (14N, 2n+2p) 69Ge 67 Zn (a, 2n) 69Ge nat Cu (p, x) 69Ge nat Zn (a, x) 69Ge 68 Zn (a, 3n) 69Ge 68 Zn (He3, 2n) 69Ge nat Zn (He3, x) 69Ge 66 Zn (a, n) 69Ge 69 Ga (a, x) 69Ge nat Ga (d, x) 69Ge 69 Ga (d, 2n) 69Ge 69 Ga (p, n) 69Ge nat Ga (p, x) 69Ge 71 Ga (p, 3n) 69Ge 70 Ge (n, 2n) 69Ge nat Ge (d, x) 69Ge nat 70 Ge (a, x) 69Ge 70 Ge (p, x) 69Ge Ge (p, n+p) 69Ge 2.6.2. Nuclear Reactions Selected for Evaluation The nuclear reactions which are evaluated in this work are given below: 66 Zn (a, n) 69Ge 67 Zn (a, 2n) 69Ge 69 Ga (d, 2n) 69Ge 69 Ga (p, n) 69Ge 71 Ga (p, 3n) 69Ge The experimental detail of these reactions is given by the following tables: Table 2.3 Experimental details of 66Zn (a, n)69Ge Author, Publication year & Reference Details of Sample Levkovskij (1991)  95 – 98% isotopically natMo (a, enriched x)97Ru target was used. - 38 7.8 – 37.7 Abu Issa et al. (1989)  66 - 11 14.8 – 24.4 13.0 31 10.7 – 37.9 Nagame et al. (1989)  Zn enriched was used. 99.8% isotopically pure & enriched targets were used. Monitor Reactions Gamma Intensity Normalization Cross Energy Factor Section Range points Author NuDat (MeV) 2.8 - - Table 2.4 Experimental details of Author, Publication year & Reference Levkovskij (1991)  Abu Issa et al. (1989)  Details of Sample 67Zn Monitor Reactions 95 – 98% isotopically natMo (a, enriched x)97Ru targets were used. Selfsupporting 67 Zn was used. (a, 2n)69Ge Gamma Intensity Normalization Cross Energy Factor Section Range points Author NuDat (MeV) 2.8 - 38 15.0 – 46.0 - 11 16.4 24.4 Table 2.5 Experimental details of 68Zn (a, 3n) 69Ge Author, Publication year & Reference Details of Sample Levkovskij (1991)  95 – 98% isotopically enriched targets were used. Monitor Reactions Gamma Intensity Normalization Cross Energy Factor Section Range points Author NuDat (MeV) 2.8 - nat Mo (a, 97 x) Ru 23 28.9 – 46.0 Table 2.6 Experimental details of 69Ga (d, 2n)69Ge Author, Publication year & Reference Baron et al. (1963)  Details of Sample Monitor Reactions Natural 27 isotopic Al (d, p + composition a)24Na of different 209Bi (d, p) 210 elements Bi and compounds were used. Gamma Intensity Normalization Cross Energy Factor Section Range points Author NuDat (MeV) 2.8 - 1 18.8 Table 2.7 Experimental details of 69Ga (p, n)69Ge Author, Publicatio n year & Reference Details of Sample Monitor Reaction s Gamma Intensity Autho r Levkovskij (1991)  Johnson et al. (1964)  Porile et al. (1963)  Blosser et al. (1955)  95 – 98% isotopically enriched targets were used. Targets were electroplated onto platinum/gol d foils. 98.4% 69Ga deposited on aluminum. Finely ground mixture of Cu-oxide and Ga-fluoride. 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