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Quantitative Bone Scintigraphy. a Study in Patients with Prostatic Carcinoma

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Quantitative Bone Scintigraphy. a Study in Patients with Prostatic Carcinoma i Quantitative Bone Scintigraphy A study in patients with prostatic carcinoma Gunilla Sundkvist \OO -II , Malmö 1991 Organization Document name LUND UNIVERSITY DOCTORAL DISSERTATION Department of Clinical Physiology Date of issue Malmö Allmänna Sjukhus 1991-05-08 S-214 01 Malmö, Sweden CODEN: LUMEDW-f.MEFM-lOlOU-lOO (1991) Authors) Sponsoring organization Gunilla Sundkvist Title and subtitle Quantitative Bone Scintigraphy. A study in patients with prostatic carcinoma. Abstract Quantitative bone scintigraphy was performed in patients with prostatic carcinoma before orchiectomy as well as two weeks, two and six months after operation. The count rate was recorded as serial gamma camera images over the lower thoracic and all lumbar vertebrae from 1 to 240 min and at 24 h after injection of "Tcm-MDP. In almost all abnormal vertebrae an increased count rate was observed within one hour after injection. Most of the vertebrae which were considered normal at 4 h after injection, but had an increased 24 h/4 h ratio developed into abnormal vertebrae later in the study. The patients with normal bone scintigrams showed no change in "Tcm- MDP uptake during the study. The reproducibility of quantitative bone scintigraphy was found to be ± 7% (1 SD). In response to therapy, most of the patients with abnormal bone scintigrams showed an increase in count rate two weeks after operation followed by a decrease to the pre-operative level after two months and a o further decrease after six months. This so called "flare phenomenon" was found to m ta indicate "Tc -MDP in the vascular phase as well as an active bone uptake. In some of the patients the whole-body retention of "Tcm-MDP after 24 h and the bone Is mineral density in the vertebrae were determined and found to be valuable in the a- * interpretation of skeletal metastases and the assessment of response to therapy. 81 *^w Prostatic Neoplasms, Bone Neoplasmp, Thoracic Vertebrae, Lumbar Vertebrae, Orchiectomy, Radionuclide Imaging Gasification system and/or index tenns (if any) Supplementary bibliographical information •fKliish ISSN and fcry title ISBN Recipient'i notes Number of pages JJJ Price Security clarification Distribution by (name and address) Department cf Clinical Physiology. Malmö Allnänna Sjukhus, S-214 01 Malmö, Sweden. I, the undersigned, being the copyright owner of the abstract of the above-mentioned dissertation, hereby grant to all reference sources permission to puMiafa and disseminate the abstract of the above-mentioned dissertation. Signature Date 1991-03-01 Quantitative Bone Scintigraphy A study in patients with prostatic carcinoma Akademisk avhandling som med vederl ^ligt tillstånd av Medicinska Fakulteten vid Lunds Universitet för avläggande av -doktorsexamen i medicinsk vetenskap kommer att offentligen försvaras i Kl i. ;kt Fysiologiska Avdelningens föreläsningssal, Allmänna Sjukhuset, Malmö, onsda; n den 8 maj 1991 kl. 9.00 av Gunilla Sundkvist Departments of Clinical Physiology and Radiation Physics, Lund University, Malmö Allmänna Sjukhus, Malmö, Sweden Quantitative Bone Scintigraphy A study in patients with prostatic carcinoma Gunilla Sundkvist Malmö 1991 ISBN91-628-0250-X © Gunilla Sundkvist Printed in Sweden Lund 1991 To Lennart Carolina, Cornelia and Christina This thesis is based on the following papers, referred to in the text by their Roman numerals: I. Sundkvist GMG, Ahlgren L, Lilja B, Mattsson S, Abrahamsson PA, Wadström LB: Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy. Eur J Nucl Med 1988; 14:203-206. II. Sundkvist GMG, Ahlgren L, Lilja B, Mattsson S, Abrahamsson PA: Dynamic quantitative bone scintigraphy in patients with prostatic carcinoma treated by orchiectomy. Eur J Nucl Med 1990; 16:671-676. III. Sundkvist GMG, Ahlgren L, Lilja B, Mattsson S: Additional information from quantitative 24-hour ""^Tc-MDP bone scintigraphy in patients with prostatic carcinoma. Accepted for publication in Acta Oncol. IV. Sundkvist GMG, Ahlgren L, Lilja B, Mattsson S: Quantitative bone scintigraphy and 24-hour whole-body counting of 99mTc methylene diphosphonate in patients with prostatic carcinoma. Submitted. V. Sundkvist GMG, Nilsson M, Ahlgren L, Lilja B, Mattsson S, Birch- Iensen M, Abrahamsson PA: Relation between 99Tcm-MDP uptake and bone mineral density in patients with prostatic carcinoma. Accepted for publication in Nucl Med Commun. Contents Abbreviations 9 Introduction 11 Historical background 11 Bone scintigraphy 12 Whole-body counting 13 Quantitative computed tomography 14 The metastatic process 14 Prostatic carcinoma 16 Mechanism of bone metastasis in prostatic carcinoma 16 Morphological aspects of vertebral metastases in prostatic carcinoma 17 Orchiectomy 18 Aims of *he Study 19 Materials and Methods 20 Patients with prostatic carcinoma 20 Control group 21 Dynamic quantitative bone scintigraphy 21 Correction procedures 23 Time-count rate curves 24 Routine whole-body scintigraphy 24 Whole-body counting 25 Quantitative computed tomography 25 Statistical methods 26 Results 27 Quantitative bone scintigraphy in the control group 27 Quantitative bone scintigraphy in patients with prostatic carcinoma before orchiectomy 29 Quantitative bone scintigraphy in patients with prostatic carcinoma after orchiectomy 30 Quantitative bone scintigraphy in relation to whole-body counting in a control group and in patients with prostatic carcinoma before and after orchiectomy 32 Quantitative bone scintigraphy in relation to quantitative computed tomography in patients with prostatic carcinoma at the time of orchiectomy and post-operatively 33 Discussion 34 Summary and Conclusions 39 Acknowledgements 41 References 42 Papers I-V 51 8 Abbreviations BMD bone mineral density MDP methylene diphosphonate ROI region of interest QCT quantitative computed tomography QS quantitative bone scintigraphy WBC whole-body counting WBR whole-body retention Introduction Historical background The discovery of artificially induced radioactivity was made by Joliot and Curie in 1934. One year later, Chiewitz and de Hevesy used the radionuclide, phosphorus-32 (32P), in the study of bone metabolism in rats. Treadwell et al. demonstrated in 1942 that strontium-89 (89Sr) accumulated chiefly in growing bone and in osteogenic tumour tissue in man. Mulry and Dudley found in 1951 that early metastases to bone could be identified through the use of gallium-72 (72Ga) before changes could be visible roentgenographically. Bauer and Wendeberg used in 1959 calcium-47 (47Ca) and strontium-85 (85Sr) in the study of localized skeletal lesions. Blau etal. found in 1962 that the uptake of fluorine-18 (18F)in normal bone is very low compared to sites of active osteogenesis. Charkes et al. employed strontium-87m (g7Srm) in 1964 in the detection of bone metastases. However, the above mentioned radionuclides showed serious limitations in the clinical use, related to radiation absorbed dose, physical or pharmacologic properties and economic factors. The introduction of the technetium-99m (99Tcm) complex of tripolyphosphate with more favourable characteristics was made in 1971 by Subramanian and McAfee. Some years later, the 99Tcm complex of methylene diphosphonate was proposed as a new skeletal imaging agent (Subramanian et al. 1973). The available evidence has suggested that the technetium-99m diphosphonates adsorb onto the surface of hydroxyapatite crystals (Francis 1969; Jones et al. 1976). Although the precise mechanism is still not completely understood, the radio- pharmaceutical is widely used. 11 In 1951 Cassen et al. invented the automatic scanner and one year later the gamma-ray pinhole camera was constructed by Anger (1952). In combination with the parallel-hole collimator (Johansson and Skanse 1953), gamma camera technology has undergone an intensive development during the last decades. The routine use of computers to acquire, process, display and store images has expanded the utility of the gamma camera, which has led to an important improvement in the imaging technique. Bone scintigraphy Bone scintigraphy is a useful method in the examination of the skeleton. Areas of abnormally increased uptake may represent skeletal involvement by tumours, metabolic or inflammatory diseases, Paget's disease or trauma (Thrall and Burton 1987). The routine bone scintigraphy is normally performed 3-4 hours after injection of 99Tcm-MDP and qualitatively interpreted. Visually, a generalized increased uptake in the skeleton may be misinterpreted as normal. Also, it may be difficult to identify lesions in which the radionuclide concentration is only slightly higher than in surrounding bone (Citrin etal. 1974). Quantification of the radionuclide uptake may then provide a more objective evaluation of the scintigram (Hardy eta). 1980), For detection of skeletal metastases bone scintigraphy is a sensitive method (Osmond et al. 1975). In patients with newly diagnosed non- osseous primary tumours with bone metastases (especially carcinoma of the breast, lung and prostate) the determination of bone involvement and 12 definition of its extent is important for staging and management. Bone scintigraphy is especially useful in early detection of metastases. When the tumour cells invade the bone, remodelling results in changed skeletal metabolism with increased tracer localization (Galasko 1977). Bone scintigraphy is, however, a non specific method (Corrie et al. 1988) and it may be difficult to distinguish between uptake due to benign or malignant processes. It is therefore of special
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