The use of radioactive nuclides in the investigation of malignant disease. A laboratory and clinical evaluation of the 99mTc phosphates as bone scanning agents in the detection of skeletal metastases

Citrin, Dennis Lionel (1975) The use of radioactive nuclides in the investigation of malignant disease. A laboratory and clinical evaluation of the 99mTc phosphates as bone scanning agents in the detection of skeletal metastases. PhD thesis, University of Glasgow.

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The relative Insensitivity of standard radiological methods in the diagnosis of early metastatic disease of the skeleton is well recognised. The development is the 1960's of isotope bone scanning using 85Sr, 87mSr and 18F permitted the earlier and more accurate diagnosis of malignant Involvement of bone, but as none of these radionuclides was ideal the technique of bone scanning has not been optimally applied in clinical medicine and surgery. In 1972 and 1973, new radiopharmaceuticals were developed which have made available to all hospitals with even limited facilities the capacity to obtain high quality bone scans. These new radiopharmaceuticals are the 99mTc labelled phosphates. This thesis describes the laboratory and clinical evaluation of the available 99mTc phosphate compounds. The introductory section describes the principle of the bone scan and how it differs from the radiograph. There follows a description of the conventional bone scanning agents 85Sr, 87mSr and 18F, and a brief discussion of the disadvantages of each of these nuclides. The development of the 99mTc phosphates is then described and the relevant physical and chemical properties of these agents is summarised. The choice of which of the available 99mTc phosphates, ethane hydroxy diphosphonate, pyrophosphate, polyphosphate and monofluorophosphate, is the most suitable agent depends on a comparison of their pharmacological properties, as they are all very similar chemically and all utilise the same radionuclide, 99mTc. The second section of the thesis describes a detailed quantitative comparison of the pharmacological properties of each compound. Several new investigative techniques were developed for this study and these techniques are described in detail. On the basis of the comparative studies, it was concluded that ethane hydroxy diphosphonate is the most favourable agent, because of the higher target: background ratios it provides, and because of its more rapid blood clearance, greater urinary excretion and lower whole body retention. A detailed evaluation of the in vitro and in vivo properties of ethane hydroxy diphosphonate is then described. The in vitro properties studied are those which are of importance to the use of the compound in routine clinical use. It was concluded that the compound is very flexible and that high quality images can be obtained despite the variation in presentation, labelling and injection procedures which may occur in a busy Department of Nuclear Medicine. The in vivo experirnejits performed in volunteer subjects and in patients with Imown bony metastases demonstrate that E.H.D.P. clearly satisfies the important biological, criteria necessary for a satisfactory bone scanning agent, namely (1) rapid skeletal uptake of a significant proportion of the administered activity. (2) skeletal binding which irreversible, in the short term at least. (3) higher uptake in tumor-involved compared with normal bone. (4) no significant retention in soft tissue. (5) rapid urinary excretion of the diphosphonate not taken up by bone. (6) lack of toxicity. The clinical sections of the thesis are introduced with a discussion of the problems of technique and scan interpretation which are particularly relevant to the 99mTc phosphates. The study performed to assess the sensitivity and clinical value of the 99mTc phosphate bone scan in patients with malignant disease is then described: three hundred and seventy two patients and 75 control subjects were studied and the results support the conclusion that the 99mTc phosphate bone scan allows earlier and more accurate identification of bone metastases than the radiograph. If the bone scan is read with all clinical details and the results of complementary radiographs available, the incidence of false positive results is acceptably low. The application of the 99mTc phosphate bone scan to the preoperative staging and clinical follow up of patients with breast cancer is described in the next section. The high incidence of bony metastases in patients with breast cancer is well recognised and the value of a technique which permits the identification of metastases in asymptomatic patients with normal radiographs is potentially great. Previous studies with strontium and fluorine have suggested that about 20% of patients with apparently curable breast cancer (Stages I and II) have bone metastases at the time of first presentation, and a similar incidence of occult metastases was observed in our study using 99mTc phosphates. The clinical importance of this study is discussed. The thesis concludes with a brief discussion of future developments in the use of isotope methods in the study of malignant disease of the skeleton. Technical improvements in scanning equipment and available radiopharmaceuticals have been significant, and the need now is for critical clinical studies which utilise the isotope bone scan to improve the diagnosis and management of patients with malignant disease of the skeleton.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: E M McGirr
Keywords: Nuclear physics and radiation
Date of Award: 1975
Depositing User: Enlighten Team
Unique ID: glathesis:1975-72657
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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