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Background: (177)Lu-(DOTA0,Tyr3) octreotate is a new treatment modality for disseminated neuroendocrine tumors. According to a consensus protocol, the calculated maximally tolerated absorbed dose to the kidney should not exceed 27 Gy. In commonly used dosimetry methods, planar imaging is used for determination of the residence time, whereas the kidney mass is determined from a computed tomography (CT) scan.Methods: Three different quantification methods were used to evaluate the absorbed dose to the kidneys. The first method involved common planar activity imaging, and the absorbed dose was calculated using the medical internal radiation dose (MIRD) formalism, using CT scan-based kidney masses. For this method, 2 region of interest locations for the background correction were investigated. The second method also included single-photon emission computed tomography (SPECT) data, which were used to scale the amplitude of the time-activity curve obtained from planar images. The absorbed dose was calculated as in the planar method. The third method used quantitative SPECT images converted to absorbed dose rate images, where the median absorbed dose rate in the kidneys was calculated in a volume of interest defined over the renal cortex.Results: For some patients, the results showed a large difference in calculated kidney-absorbed doses, depending on the dosimetry method. The 2 SPECT-based methods generally gave consistent values, although the calculations were based on different assumptions. Dosimetry using the baseline planar method gave higher absorbed doses in all patients. The values obtained from planar imaging with a background region of interest placed adjacent to the kidneys were more consistent with dosimetry also including SPECT. For the accumulated tumor absorbed dose, the first 2 of the 4 planned therapy cycles made the major contribution.Conclusions: The results suggested that patients evaluated according to the conventional planar-based dosimetry method may have been undertreated compared with the other methods. Hematology and creatinine did not indicate any restriction for a more aggressive approach, which would be especially useful in patients with more aggressive tumors where there is not time for more protracted therapy. [ABSTRACT FROM AUTHOR]

The radiobiological effect of intracellularly localised radionuclides emitting low energy electrons (Auger electrons) has received much attention. Most in viva studies reported have been performed in the mouse testis. We have investigated the rat testis as an in viva radiobiological model, with sperm-head survival, testis weight loss and also alteration in the blood plasma hormone levels of FSH and LH as radiobiological endpoints. Validation of the rat testis model was evaluated by using mean absorbed doses of up to 10 Gy from intratesticularly (i.t.) injected 111In oxine or local X-ray irradiation. Biokinetics of the i.t. injected radionuclide was analysed by scintillation camera imaging and used in the absorbed dose estimation. By the analysis of the autoradiographs, the activity distribution was revealed. Cell fractionation showed 111In to be mainly associated with the cell nuclei. External irradiations were monitored by thermoluminescence dosimeters. The sperm-head survival was the most sensitive radiobiological parameter correlated to the mean absorbed dose, with a D37 of 2.3 Gy for 111In oxine and 1.3 Gy for X rays. The levels of plasma pituitary gonadal hormones FSH and LH were elevated for absorbed doses >7.7 Gy. This investigation shows that the radiobiological model based on the rat testis has several advantages compared with the previously commonly used mouse testis model. The model is appropriate for further investigations of basic phenomena such as radiation geometry, intracellular kinetics and heterogeneity, crucial for an understanding of the biological effect of low-energy electrons. [ABSTRACT FROM AUTHOR]

Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p = 0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines. [ABSTRACT FROM AUTHOR]