In our series, diffuse heterogeneous brain hypoperfusion is often the sole early objective imaging feature identified by SPECT of high-dose ara-C neurotoxicity, where MRI still demonstrates normal pictures.
Between 1943 and 1965, 359 patients with carcinoma of the thyroid were treated by external radiotherapy or radioiodine out of a total number of 560 patients treated during the same period. In 65 of these patients surgery had been satisfactory from a macroscopic point of view. Prophylactic post-operative irradiation was given to 55 and the survival rate was 91 per cent at five years and 85 per cent at ten years. Ten received radioiodine, eight were alive at five years and six at ten years. In 95 patients excision of the tumour had been macroscopically incomplete. Fifty-four were treated by external radiotherapy and the survival rates were 50 per cent at five years and 48 per cent at ten years. For the differentiated carcinoma of this group 68 per cent were surviving at five years and 58 per cent at ten years. Of 41 patients treated with radioiodine, 75 per cent were surviving at five years and 31 per cent at ten years. Eighty-five patients were inoperable. Sixty were treated by external radiotherapy, the survival rates were 17 per cent at five years and 8.5 per cent at ten years. For the differentiated carcinomas of this group the survival rates were 24 per cent and 18 per cent. Twenty-five were treated with radioiodine, 26 per cent were surviving at five years and 4.5 per cent at ten years. The patients treated by external radiotherapy can be divided into two subgroups according to the technique of treatment and dose used. Between 1943 and 1955, patients were treated with conventional X rays (mean applied dose 2,800 rads), between 1956 and 1965 the patients were treated with 60Co (mean applied dose 5,000 rads). For the 45 patients of the first group, the survival rates were 35 per cent at five years and 32 per cent at ten years. For the 124 of the second group the respective survival rates were significantly higher: 60.6 per cent and 53 per cent. The results of external radiotherapy were similar to those of radioiodine at five years and better at ten years. In conclusion, a dose of 5,000 to 6,000 rads delivered by megavoltage external radiotherapy in five to six weeks, is well tolerated and effective mostly in differentiated carcinomas and medullary carcinomas. The survival rates of 64 patients whose metastases were unable to pick up iodine is practically zero at five years. For 68 patients with uptake in their metastases the survival rates were 53 per cent at five years and 23 per cent at ten years. The survival rate in patients with pulmonary metastases was higher than in patients with bony metastases (75 per cent versus 44 per cent at five years and 42 per cent versus 8 per cent at ten years.
The radionuclides used in nuclear medicine imaging emit numerous mono-energetic electrons responsible for dose heterogeneity at the cellular level. S(self) the self-dose per unit cumulated activity (which results from the radionuclide located in the target cell), and S(cross) the cross-dose per unit cumulated activity (which comes from the surrounding cells) delivered to a target cell nucleus by electron emissions of technetium-99m, iodine-123, indium-111, gallium-67 and thallium-201 were computed at the cellular level. An unbounded close-packed hexagonal cell arrangement was assumed, with the same amount of radioactivity per cell. Various cell sizes and subcellular distributions of radioactivity (nucleus, cytoplasm and cell membrane) were simulated. The results were compared with those obtained using conventional dosimetry. S(self) and S(cross) values depended closely on cell dimensions. While the self-dose depended on the tracer distribution, the latter affected the cross dose by less than 5%. When the tracer was on the cell membrane, the self-dose was particularly low compared to the cross-dose, as the self-dose to cross-dose ratio was always less than 11%. In the case of cytoplasmic or cell membrane distribution of radioactivity, conventional electron dosimetry slightly overestimated the dose absorbed by the target cell nucleus (by 1.08-to 1.7-fold). In contrast, conventional dosimetry strongly underestimated the absorbed dose (1.1- to 75-fold) when the radioactivity was located in the nucleus. The discrepancies between conventional and cellular dosimetry call for calculations at the cellular level for a better understanding of the biological effects of radionuclides used in diagnostic imaging.
The mean dose delivered to the cell nucleus by electron emissions of 99Tcm, 123I, 111In, 67Ga and 201Tl was evaluated at the subcellular level. Models were applied assuming uniform distributions of radioactivity throughout the nucleus, the cytoplasm or the cell membrane, allowing computation of the total absorbed fraction, phi and S-values to the cell nucleus as a function of cell dimensions. The graphs of phi plotted according to cell dimensions show that the dose to the cell nucleus strongly depends on the subcellular distribution of radioactivity, the nucleus radius Rnucl and the cytoplasmic thickness e. For a nuclear distribution, phi ranges from 0.1 to 0.35 for the radionuclides studied and S from 0.049 cGy Bq-1 s-1 to 5.503 cGy Bq-1 s-1. In the case of a cell membrane localization, the maximum is obtained for 123I (phi = 0.016). For a cytoplasmic distribution, the maximum is obtained for 201Tl with a value of 0.036. To ease future calculations, third-degree polynomials have been separately fitted to the relationship between the mean absorbed dose to the nucleus for activity accumulated in the nucleus, cytoplasm or surface of the cell membrane. We found a good agreement between our computations and the values obtained by the polynomials. The relative difference between the two methods is always less than 0.7%, 2.8% and 4.5% respectively for nuclear, cell membrane and cytoplasmic distributions.
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