I= PREPARATION OF NEW RADIOPHARMACEUTICALS THEIR BIOCHEMICAL AND PHARMACOKINETIC STUDIES
Pakistan Research Repository Home
 

Title of Thesis
PREPARATION OF NEW RADIOPHARMACEUTICALS THEIR BIOCHEMICAL AND PHARMACOKINETIC STUDIES

Author(s)
Faiz-ur-Rehman
Institute/University/Department Details
Institute of Chemistry University of the Punjab
Session
1985
Subject
Chemistry
Number of Pages
225
Keywords (Extracted from title, table of contents and abstract of thesis)
RADIOPHARMACEUTICALS, radio nuclide, Tc99m-pertechnetate, TC99m-pyridoxal-mimosine,TC99m-tin-monomercaptosuccinic acid, TC99m-tin-phosphate, TC99m-tin-phosphate polyvinyl pyrollidone, TC99m (Sn) thioglycolide aminates

Abstract
Radiodiagnostic agents were developed for investigation of various diseases of kidney, reticuloendothelial system, heart and tumour. Chemicals of clinical interest were labelled with Tc99m and characterised using techniques like electro-phoresis, chromatography, electron microscopy, coulter counter, UV spectroscopy and animal studies. Preparations obtained were optimized to obtain anatomical, physiological, pharmacological or biochemical information to make them more organ specific.

Complexes of B-[N-(3-Hydroxy-4-Pyridone)]-α-amino propionic acid (mimosine) and monomercaptosuccinic acid(MMSA) labelled with Tc99m were prepared for renal studies by autoclave and tin reduction method. Mimosine possessing α amino acid group was complexed with Tc99m through Schiff's base formation by pyridoxal hydrochloride. Monomercaptosuccinic acid was complexed with Tc99m by mixing (Sn-MMSA) reagents solution with Tc99m pertechnetate. Upon biodistribution studies in rabbits monomercaptosuccinic acid complex was found better than mimosine for renal studies because of its renal uptake, blood disappearance and dynamic behaviour. Its chelate with Tc99m was found more stable and nontoxic. Complex of captosuccinic acid when compared with I131-hippuran, monomer-a typical renal agent was found clinically more informative in describing various diseased states of kidney. Normal human study of mono-mercaptosuccinic acid complex showed 30±5% excretion in urine in one hour and above 95% at 24 hours. However, the clinical utility of the complex was established by comparing with other renal agents reported earlier.

New radiocolloid was developed and designed for liver/spleen imaging by "sizing" the colloidal preparations using various techniques of filteration, gel chromatography and Coulter counter. Tc99m -tin phosphate colloid was prepared and determined its stability, particle size, mobility, charge density and distribution in the reticuloendothelial system. Particle size was found ranging 100 nm - 1μ. Mobility and charge density determined by Burton Tube Method was 0.195 cm2/ V. Secx104 and 1.25 esu cm2x10-3 respectively. However distribution of the colloid in mice showed 85% uptake in liver and 6% in spleen, at 15 minutes with negligible activity in the renal area. Toxicity study showed a wide margin of safety for human use found by injecting larger doses to mice and rabbits. Human study in normal condition showed the results closer to the animal findings. Tc99m -tin-phosphate colloid was also evaluated in patients by injecting 3-5 mCi of dose in various diseased conditions regarding the reticuloendothelial system.

A minimicro colloid was also developed for bone marrow imaging by dilution of tin phosphate colloid and addition of polyvinyl pyrollidone (MW 40,000). Particle size was found to be in the range of 15 nm as determined by electron microscopy. Sizing of colloidal preparations was also performed by Coulter counter and microphotography. Upon biodistribution studies in rabbits high bone marrow uptake (27%) was indicated as compared to results reported earlier (16%). Blood disappearance occurred biexponentially with a faster phase of 4.47 minutes and a slower phase of 33.3 minutes. Normal human study showed appreciable uptake of minimicro colloid for bone marrow imaging in the areas of clinical interest.

A new method of labelling amino acids with Tc99m was designed by reacting with thioglycolic acid and tin(II) ions. Thus complexes of dl-isoleucine, 1-lysine, phenyl alanine and l-cysteine were prepared and over 95% labelling with Tc99m was achieved as checked by paper and column chromatography. Upon biodistribution in rabbits dl-isoleucine, a branched chain amino acid showed 2.99% uptake in myocardium at one hour post-injection as compared to 2.2% in the case of Tc99m -1, 2 bis (dimethyl phosphino) ethane (DMPE) complex under study by other investigators. Tl201 in rats, a chloride, a standard myocardial imaging agent has 3.3% heart muscle uptake but with unfavourable nuclear properties.

Complex of 1-lysine was found to be excreted through hepatobiliary system (73%) at one hour without any renal uptake. Complexes of other amino acids phenylalanine and 1-cysteine were found to be renal excreting with high renal uptake 20% and 22% respectively. Both the agents were found excreting slowly in the urine and thus could be applied in renal imaging for anatomic information. However, recent studies regarding distribution of Tc99m labelled sulphur containing amino acids in various types of tumours have indicated possible use of Tc99m (Sn)-thioglycolide aminates for similar studies.

Download Full Thesis
2261.5 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
56.65 KB
2 1 Introduction
87.28 KB
  1.1 Choice of radio-nuclide for scintigraphy 4
  1.2 Pharmacokinetics of Tc99m-pertechnetate 8
  1.3 Design of new radiopharmaceuticals 9
3 2 TC 99m -pyridoxal-mimosine complex : Preparation and its use for kidney scanning
147.81 KB
  2.1 Abstract 17
  2.2 Introduction 18
  2.3 Materials and methods 21
  2.4 Results 26
  2.5 Discussion 39
4 3 TC 99m -tin-monomercaptosuccinic acid complex : preparation and biological evaluation in reanal disorder and brain tumour
305.18 KB
  3.1 Abstract 41
  3.2 Introduction 42
  3.3 Materials and methods 45
  3.4 Results 53
  3.5 Discussion 78
5 4 Preparation of TC 99m -tin-phosphate colloid and its biological evaluation for reticulo-endothelial system study
175.09 KB
  4.1 Abstract 82
  4.2 Introduction 83
  4.3 Materials and methods 86
  4.4 Results 91
  4.5 Discussion 106
6 5 Preparation of TC 99m -tin-phosphate polyvinyl pyrollidone stabilized colloid and distribution in bone marrow
147.81 KB
  5.1 Abstract 109
  5.2 Introduction 110
  5.3 Materials and methods 112
  5.4 Results 117
  5.5 Discussion 128
7 6 TC 99m ( Sn ) thioglycolide aminates-preparation and biological evaluation
1311.81 KB
  6.1 Abstract 130
  6.2 Introduction 131
  6.3 Materials and methods 133
  6.4 Results 138
  6.5 Discussion 149
  6.6 Reference 152
  6.7 Publications