[en] The absorbed dose to tumors after systemic administration of radiopharmaceuticals is not sufficient to achieve acceptable levels of probability of tumor control without compromising on critical tissue toxicity (kidney and / or bone marrow (BM)). There are reports of trials with multiple administrations, about tolerance level inter-administration intervals to allow recovery of the BM, with good results. The biokinetic behavior of some radiopharmaceuticals known makes possible the application of several administrations with short intervals of time.It is the present work combines two kinetic models of tumor growth and cell kinetics in the BM for predicting the response to continuous irradiation at low dose rate. The estimation of the effects of irradiation on tumor and kidneys was done using a formulation of the linear-quadratic model functions suitable for dose rate and multi-exponential repair. The estimation of the response in WB performed using a compartmental model previously reported. The absorbed dose to organs were calculated using the MIRD formulation taking into account the effect of irradiation cross. Biokinetic data were used for therapeutic radiopharmaceuticals 90Y, 131I and 177Lu, as well as radiobiological parameters reported for experimental animals. The effect on the response by the variation of inter-administration interval in slow-growing tumors and fast, so as the radiosensitive and radioresistant tumors. You can set conditions irradiation to an acceptable level of thrombocytopenia (onset and duration of the minimum in the curve) and renal irradiation below the limit of tolerance. It is possible to design experiments evaluation of therapeutic radiopharmaceuticals with a greater degree of refinement. (author)

[en] Measurement in a radionuclide therapy is an essential element in Nuclear Medicine practice. To assure that patient will receive the optimal doses that guarantee the necessary quality of the image to be studied or optimum radiotherapeutic effect, the activity determination should carry out established accuracy requirements. A treatment planing system could be obtained by means of: 3D patient-specific dosimetry models based on SPECT imaging, tools for treatment optimization (DVH, Dose statistic, Isodose surface), dose-response model for single and multiple activity administrations. The next step is establish the reference conditions for validation and verification of the accuracy of internal dose calculations by direct measurement of dose using anthropomorphic phantoms

[en] Notwithstanding the limitations of radiobiological models in the clinical application, its use is becoming more widespread in order to quantitatively assess the bioequivalence of different regimens of irradiation, the effective comparison between different treatment plans by estimating the probability tumor control (TCP) or the probability of normal tissue complication (NTCP), or solve problems, such as the rescheduling of treatments in case of failure. The response to irradiation in the tissues at risk (OARS) depends on factors such as volume irradiated or its organizational structure and behavior can vary for a given dose distribution. Another important aspect is the sensitivity of these models to the variation of parameters (a, a / β, proliferation, clonogenic density, etc.) Measuring the difference between-subjects. Commercial planning systems do not always possible to estimate the biological response of the OARS and CTV. This study presents an assessment of the results of two applications (free ware) and Albireo Target BIOPLAN Cygnus X1 that calculate statistical parameters of the DVH: equivalent uniform dose (EUD), equivalent biological dose (BED), medium dose and other to estimate TCP (Poisson model) and NTCP (Lyman-models-Kutcker Burman and relative seriality) for the calculation of the objective functions: the probability of uncomplicated control (UTCP) based on generalized EUD (f). We studied the response of both systems to the variation of relevant radiobiological parameters and the shape of the DVH. (author)

[en] Full text: Good results for radionuclide therapy treatments where repeated short time spaced systemic injection of small activity amounts are given have been reported. Bone marrow and kidneys are usually considered as dose-limiting organs in radionuclide therapy. The treatments in radionuclide therapy with repeated administration could be optimized if irradiation effects in those one might be estimated. Xeno-grafted mice is the often biological model used during the evaluation of candidates for radionuclide therapy. A mathematical model of tumor cell kinetics was combined with another one reported for marrow cell kinetics which allows the calculation of marrow cell survival and proliferation in response to different irradiation schemes. Radionuclide therapy treatment with repeated administrations with radiopharmaceuticals labeled with beta emitters were simulated. The effects on fast-growing and slow-growing tumors were evaluated, as well as radiosensitive and radioresistant tumors. For more realistic estimation of absorbed dose in mice organs the cross-irradiation due to high energy beta particles was included into the MIRD's formula. Tumor and kidneys responses to the irradiation were estimated on the linear-quadratic model framework which was adapted for a multi-exponential dose rate function describing radionuclide therapy treatments with repeated administrations. Published values for murine tumors kinetics, marrows cellular turnover rates and radiosensitivities were used during the calculations. Iso-effective schemes were also determined varying the interval between fractions and the number of administration. For a given tolerated level of thrombocytopenia and absorbed dose in kidneys an optimal regime of radionuclide therapy with repeated administration could be found. The mathematical model presented here allows the prediction of the nadir and duration of thrombocytopenia, the effects on kidneys and the tumor cell response to various treatment schemes in radionuclide therapy with repeated administrations closer to real experiments. The model can be used for the determination of injected activity per fraction for refined experiments in radionuclide therapy for different situations during preclinical evaluations of radiopharmaceutical for therapy. (author)

[en] Full text: As the sizes of mouse organ are comparable with the range of the high-energy beta particles emitted by the radionuclides commonly used in radionuclide therapy a significant amount of beta radiation emitted could be imparted to the adjacent tissues. The often assumption that beta particles are fully-absorbed at the emission site is not satisfied and cross-irradiation should be included into the dose estimation formulas. Keeping in mind that the radiation effects are correlated with the absorbed dose in the target the inclusion of cross-irradiation in the dose estimation must be evaluated. The MIRD's formulation was used to perform absorbed dose calculation in mice using absorbed fractions previously reported for ¹³¹I, ⁹⁰Y and ¹⁷⁷Lu. Two approaches were considered: a) cross irradiation when a fraction of beta particles emitted can escape from the organ source and, b) full self- irradiation when the beta particles are considered fully absorbed at the emission site. The formulation of linear-quadratic model was readapted to be used in the radionuclide therapy. Treatment with a single administration in mice was simulated and radiation effects on tumor, bone marrow and kidneys under the assumption of cross-irradiation were predicted. A biphasic repair kinetics was considered in the calculation of irradiation effects on kidneys. Typical published biokinetic data for radiopharmaceutical assayed in mice and radiobiological parameters were used in the calculations. The influence of cross irradiation condition was diverse for the tissues analyzed here. The absorbed dose values in kidneys calculated for both methods were no significantly different for low energies, but variations around to 40-50% (over or under-estimation) in absorbed dose were obtained for high energies. Approximately a 30% of the beta radiation emitted from bone will cross irradiates the bone marrow. For injected activities values higher than 10MBq (300μCi), as a single injection, the absorbed dose in BM exceeds the tolerable limits (2Gy). The formulation presented here could be used in the design of refined experiments for radionuclide therapy with mice model where the radio myelotoxicity and/or toxicity in kidneys needs to be controlled. (author)

[en] Notwithstanding the limitations of radiobiological models in the clinical application, its use is becoming more widespread in order to quantitatively assess the bioequivalence of different regimens of irradiation, the effective comparison between different treatment plans by estimating the probability tumor control (TCP) or the probability of normal tissue complication (NTCP), or solve problems, such as the rescheduling of treatments in case of failure. The response to irradiation in the tissues at risk (OARS) depends on factors such as volume irradiated or its organizational structure and behavior can vary for a given dose distribution. Another important aspect is the sensitivity of these models to the variation of parameters (α, α / β, proliferation, clonogenic density, etc.) Measuring the difference between-subjects. Commercial planning systems do not always possible to estimate the biological response of the OARS and CTV. This study presents an assessment of the results of two applications (free ware) and Albireo Target BIOPLAN Cygnus X1 that calculate statistical parameters of the DVH: equivalent uniform dose (EUD), equivalent biological dose (BED), medium dose and other to estimate TCP (Poisson model) and NTCP (Lyman-Kutcker models-Burman and relative seriality) for the calculation of the objective functions: the probability of uncomplicated control (UTCP) based on generalized EUD (f). We studied the response of both systems to the variation of relevant radiobiological parameters and the shape of the DVH. (Author)

[en] Medication mistakes in case of chemotherapy or adjuvant treatment used in any stage of drug application process: prescription, transcription, preparation, dispense or administration, are a frequent cause of side effects of antineoplastic drugs. (Author)

[en] Radioimmunotherapy has a growing interest as a new potential modality for cancer treatment. In this paper several aspects are discussed: effectiveness of radioimmunotherapy, the procedures to get dosimetric information, the appropriate radionuclide and the possibilities and limitations that dosimetric estimation methods offer. A detailed study about radiobiological models which can be used for dose prescription is also presented (Au)

[en] Full text: The 14F7 murine MAb is an IgG1 that binds specifically to GM3(Neu-Gc) ganglioside strongly recognizing the antigen displayed in human breast and melanoma tumors. A preliminary report showed in vivo evidences of presence of GM3(Neu-Gc) ganglioside in human breast primary tumors using 14F7 MAb labelled with ^99mTc. In this work the pharmacokinetics and biodistribution of ^99mTc-14F7 MAb in patient with breast cancer were studied. The absorbed dose in normal organ and tumors was also calculated. The patients were selected from a Phase I/II clinical trial which included 14 female patients with cytological diagnose of breast carcinoma in stage II without previous onco-specific treatment. Three groups were conformed: Group I (0.3mg, n=5), Group II (1mg, n=5) and Group III (3mg, n=4). The activity ranged in 1.11 - 1.48GBq (30- 40mCi) was intravenously administered during 1-2min. The ^99mTc-14F7 plasma clearance was determined by blood sampling at 5, 10, 20, 30min and 1, 2, 4, 8 and 24h after injection. All urine excreted by patients was collected during 24h after injection at intervals of 0-2h, 2-8h and 8-24h. Prior to injection, a transmission scan of head, thorax, abdomen and pelvis was obtained using a ⁵⁷Co flood source. Anterior and posterior whole body images were acquired at 30min, 2h, 4h, 8h and 24h after injection using a Gamma Camera (SophyCamera DS7) with pinhole collimator. Static anterior and posterior images were obtained from head, thorax, abdomen, pelvis and lateral images of each breast in pendular position at 2h, 4h, 8h and 24h. Internal absorbed dose calculation was performed according to MIRD formalism using the S values for adult non-pregnant female phantom downloaded from the RADAR website. Self-absorbed tumor dose were calculated assuming those as spheres with uniform distribution of activity. The plasma clearance of radiotracer in all groups shows a monoexponential decay behaviour with biological elimination half time ranged in 15h and 19h. The distribution volume was similar to physiological volume in normal subject. A low urinary excretion was observed. The biodistribution shows a high retention of radiotracer in whole-body. A high uptake and retention was observed in bone marrow, kidneys and liver. The highest absorbed dose per MBq was observed in liver and kidneys. The ^99mTc-14F7 shows a rapid tumor uptake (<2.5h) with a delayed biological elimination half time (>4.5 days). In most cases, the maximum activity uptake in tumor (<1%/100g of tumor) was observed at 24 hours after injection. The pharmacokinetic data observed for ^99mTc-14F7 MAb behaves as a monoexponential model showing a slow clearance from plasma and a low urinary excretion. (author)

[en] Neuroendocrine tumours are neoplasms that arise from various tissues closely linked to the neural crest by their common embryological origin. These tumours have the ability to synthesize neurotransmitter peptides and hormones, as well as to store catecholamines. Some of these tumours express somatostatin receptors at their membranes, what have allowed nuclear medicine to be involved in their diagnosis, treatment and monitoring. Since they arise from different and varied types of tissues, these tumours have a wide range of signs and symptoms different for every one of them. These signs and symptoms mainly depend on their biochemical characteristics, given by the substances they secrete, as well as by their location, and consequently, they also depend on the place where the tumour appears, its local infiltration, and potential long-distance metastasis resulting from the tumour). Neuroendocrine tumours are diagnosed by means of nuclear medicine images, which are obtained by using different techniques and radiopharmaceuticals such as ⁹⁹mTc dimercaptosuccinic acid (DMSA(V)), ⁹⁹mTc-methoxy-isobutyl-isonitrile (MIBI), metaiodobenzylguanidine (MIBG) labelled with ¹³¹I or ¹²³I (¹³¹I-MIBG or ¹²³I -MIBG), ¹¹¹In-labelled octreotide, positron emission tomography, using ⁶⁸Ga-labelled somatostatin analogues and carcinoembryonic antigen monoclonal antibodies. Nuclear medicine uses mainly somatostatin analogues labelled with ⁹⁰Y or ¹⁷⁷Lu for the treatment of these tumours. This paper is aimed at showing our experience in the use of ¹³¹I-MIBG for the diagnosis and treatment of neuroendocrine tumours.(author)