[en] Monoclonal antibodies TP-1 and TP-3 are of potential utility for the radioimmunodiagnosis of osteosarcoma in both human and canine patients. The V genes of these antibodies were cloned and sequenced and to facilitate radiolabeling of these proteins, the location of the lysine residues within these sequences have been determined. The V-domains of TP-1 contain a total of 12 lysines, 10 in the framework region and 2 in the CDR region, while the V-domains of TP-3 contain a total of 14 lysines, 11 in the framework region and 3 in the CDR regions. Using space-filling models, the availability of each lysine residue for radiolabeling, and potential interference with antigen binding was predicted

[en] A HPLC system has been developed for carrier free and rapid delivery in a physiological buffer of the α-particle emitting bone-seeking radiopharmaceutical ²¹²Bi-DOTMP. ²⁰⁵Bi-DOTMP was synthesized and HPLC purified to mimic and visualize the deposition pattern in bony tissues of ²¹²Bi-DOTMP by autoradiography. Inhomogeneous bone deposits were found with the highest concentration in the bone matrix, the endosteum and in the growth zones of young mice. Analysis of urine samples showed that ²⁰⁵Bi-DOTMP was cleared as an intact complex

[en] To minimize nontarget organ uptake in animals receiving radiolabeled amidobisphosphonates, the influence of pretreatment with cold 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APB, pamidronate) was studied. Three groups of animals were given pure 3-[¹²⁵I]iodobenzamide-N-3-hydroxypropylidene-3,3-bisphosphonate (IBPB) and 3-[²¹¹At]astatobenzamide-N-3-hydroxypropylidene-3,3-bisphosphonate (ABPB) (control); co-injection of APB and IBPB/ABPB; and 1 h preinjection of APB followed by IBPB/ABPB, respectively. A significant reduction of uptake in normal tissue was observed, whereas the bone uptake remained constant at 35-50%ID/g tissue. This study suggests that co- or preinjection of pamidronate may reduce the normal organ radiation doses when using these radiohalogenated bisphosphonates for endoradiotherapeutic procedures

[en] Purpose. The purpose of this study was to compare late radiation-induced radiological abnormalities of the lung with spirometric observations. Radiological abnormalities were also related to theoretical calculations, in order to predict late effects based on dose-volume histograms. Patients and methods. Sixty-one breast cancer patients who had received postoperative radiotherapy were included. During a follow-up examination 3 years or more after start of radiotherapy, computed tomography (CT) scans and pulmonary function tests were performed. Grading of radiological abnormalities (fibrosis) was performed based on CT images. Based on the dose volume histograms of the lung, effective dose was calculated. Results. There was a positive correlation between the effective radiation dose and the fraction of patients that developed radiation induced fibrosis. No significant association was found between the normalized forced vital capacity (FVC) and the radiological abnormality score or the effective radiation dose. Conclusion. In this study we found no correlation between local radiation-induced changes in the lung tissue and overall lung function. The effective dose was a better predictive factor for radiation induced fibrosis than for overall lung function

[en] Purpose: The outcome of biologic image-guided radiotherapy depends on the definition of the biologic target. The purpose of the current work was to extract hyper perfused and hypermetabolic regions from dynamic positron emission tomography (D-PET) images, to dose escalate either region and to discuss implications of such image guided strategies. Methods: Eleven patients with soft tissue sarcomas were investigated with D-PET. The images were analyzed using a two-compartment model producing parametric maps of perfusion and metabolic rate. The two image series were segmented and exported to a treatment planning system, and biological target volumes BTV_per and BTV_met (perfusion and metabolism, respectively) were generated. Dice's similarity coefficient was used to compare the two biologic targets. Intensity-modulated radiation therapy (IMRT) plans were generated for a dose painting by contours regime, where planning target volume (PTV) was planned to 60 Gy and BTV to 70 Gy. Thus, two separate plans were created for each patient with dose escalation of either BTV_per or BTV_met. Results: BTV_per was somewhat smaller than BTV_met (209 ±170 cm³ against 243 ±143 cm³, respectively; population-based mean and s.d.). Dice's coefficient depended on the applied margin, and was 0.72 ±0.10 for a margin of 10 mm. Boosting BTV_per resulted in mean dose of 69 ±1.0 Gy to this region, while BTV_met received 67 ±3.2 Gy. Boosting BTV_met gave smaller dose differences between the respective non-boost DVHs (such as D₉₈). Conclusions: Dose escalation of one of the BTVs results in a partial dose escalation of the other BTV as well. If tumor aggressiveness is equally pronounced in hyper perfused and hypermetabolic regions, this should be taken into account in the treatment planning

[en] In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO₂-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO₂-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO₂ Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO₂ values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields and step-and-shoot intensity levels). Simulated random and systematic errors in the pO₂-related images reduced the TCP for the non-uniform dose prescription. In conclusion, improved tumour control of hypoxic tumours by dose redistribution may be expected following hypoxia imaging, tumour control predictions, inverse treatment planning and IMRT

[en] Tumour hypoxia is a known cause of clinical resistance to radiation therapy. The purpose of this work was to model the effects on tumour control probability (TCP) of selectively boosting the dose to hypoxic regions in a tumour, while keeping the mean tumour dose constant. A tumour model with a continuous oxygen distribution, incorporating pO₂ histograms published for head and neck patients, was developed. Temporal and spatial variations in the oxygen distribution, non-uniform cell density and cell proliferation during treatment were included in the tumour modelling. Non-uniform dose prescriptions were made based on a segmentation of the tumours into four compartments. The main findings were: (1) Dose redistribution considerably improved TCP for all tumours. (2) The effect on TCP depended on the degree of reoxygenation during treatment, with a maximum relative increase in TCP for tumours with poor or no reoxygenation. (3) Acute hypoxia reduced TCP moderately, while underdosing chronic hypoxic cells gave large reductions in TCP. (4) Restricted dose redistribution still gave a substantial increase in TCP as compared to uniform dose boosts. In conclusion, redistributing dose according to tumour oxygenation status might increase TCP when the tumour response to radiotherapy is limited by chronic hypoxia. This could potentially improve treatment outcome in a subpopulation of patients who respond poorly to conventional radiotherapy