boron and 4-borono-2-fluorophenylalanine

In boron neutron capture therapy (BNCT) for cancer, the accurate estimation of. The maximum mean

Topics: Adult; Boron; Boron Compounds; Boron Neutron Capture Therapy; Female; Healthy Volunteers; Humans; Isotopes; Male; Middle Aged; Phenylalanine; Positron-Emission Tomography; Radiotherapy Dosage; Radiotherapy, Image-Guided; Tissue Distribution; Young Adult

To plan the optimal BNCT for patients with malignant cerebral glioma, estimation of the ratio of boron concentration in tumor tissue against that in the surrounding normal brain (T/N ratio of boron) is important. We report a positron emission tomography (PET) imaging method to estimate T/N ratio of tissue boron concentration based on pharmacokinetic analysis of amino acid probes.. Twelve patients with cerebral malignant glioma underwent 60 min dynamic PET scanning of brain after bolus injection of (18)F-borono-phenyl-alanine (FBPA) with timed arterial blood sampling. Using kinetic parameter obtained by this scan, T/N ratio of boron concentration elicited by one-hour constant infusion of BPA, as performed in BNCT, was simulated on Runge-Kutta algorithm. (11)C-methionine (MET) PET scan, which is commonly used in worldwide PET center as brain tumor imaging tool, was also performed on the same day to compare the image characteristics of FBPA and that of MET.. PET glioma images obtained with FBPA and MET are almost identical in all patients by visual inspection. Estimated T/N ratio of tissue boron concentration after one-hour constant infusion of BPA, T/N ratio of FBPA on static condition, and T/N ratio of MET on static condition showed significant linear correlation between each other.. T/N ratio of boron concentration that is obtained by constant infusion of BPA during BNCT can be estimated by FBPA PET scan. This ratio can also be estimated by MET-PET imaging. As MET-PET study is available in many clinical PET center, selection of candidates for BNCT may be possible by MET-PET images. Accurate planning of BNCT may be performed by static images of FBPA PET. Use of PET imaging with amino acid probes may contribute very much to establish an appropriate application of BNCT for patients with malignant glioma.

Topics: Algorithms; Astrocytoma; Boron; Boron Compounds; Boron Neutron Capture Therapy; Brain Neoplasms; Carbon Radioisotopes; Glioblastoma; Glioma; Humans; Methionine; Phenylalanine; Positron-Emission Tomography; Radiation-Sensitizing Agents; Radiotherapy Planning, Computer-Assisted

Positron emission tomography (PET) has become a key imaging tool in clinical practice and biomedical research to quantify and study biochemical processes in vivo. Physiologically active compounds are tagged with positron emitters (e.g. (18)F, (11)C, (124)I) while maintaining their biological properties, and are administered intravenously in tracer amounts (10(-9)-10(-12)M quantities). The recent physical integration of PET and computed tomography (CT) in hybrid PET/CT scanners allows a combined anatomical and functional imaging: nowadays PET molecular imaging is emerging as powerful pharmacological tool in oncology, neurology and for treatment planning as guidance for radiation therapy. The in vivo pharmacokinetics of boron carrier for BNCT and the quantification of (10)B in living tissue were performed by PET in the late nineties using compartmental models based on PET data. Nowadays PET and PET/CT have been used to address the issue of pharmacokinetic, metabolism and accumulation of BPA in target tissue. The added value of the use of L-[(18)F]FBPA and PET/CT in BNCT is to provide key data on the tumour extraction of (10)B-BPA versus normal tissue and to predict the efficacy of the treatment based on a single-study patient analysis. Due to the complexity of a binary treatment like BNCT, the role of PET/CT is currently to design new criteria for patient enrolment in treatment protocols: the L-[(18)F]BPA/PET methodology could be considered as an important tool in newly designed clinical trials to better estimate the concentration ratio of BPA in the tumour as compared to neighbouring normal tissues. Based on these values for individual patients the decision could be made whether BNCT treatment could be advantageous due to a selective accumulation of BPA in an individual tumour. This approach, applicable in different tumour entities like melanoma, glioblastoma and head and neck malignancies, make this methodology as reliable prognostic and therapeutic indicator for patient undergoing BNCT.

Topics: Boron; Boron Compounds; Boron Neutron Capture Therapy; Fluorine Radioisotopes; Humans; Isotopes; Lymphatic Metastasis; Melanoma; Models, Biological; Neoplasms; Phenylalanine; Positron-Emission Tomography; Prognosis; Radiation-Sensitizing Agents; Tomography, X-Ray Computed

Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.

Topics: Boron; Boron Compounds; Boron Neutron Capture Therapy; Fluorine Radioisotopes; Glioma; Humans; Isotopes; Mathematical Computing; Phenylalanine; Radiation-Sensitizing Agents; Tomography, Emission-Computed

Detection and diagnosis of human malignant melanoma by Positron Emission Tomography (PET) using 18F-10B-L-BPA, a specific melanogenesis-seeking compound synthesized for use in Boron Neutron Capture Therapy for malignant melanoma (NCT), has been developed. This resulted in a novel, highly effective methodology for the selective three dimensional imaging of metastatic malignant melanomas, and for accurate determination of 10B concentration in the tumor and surrounding tissue, providing almost all diagnostic information necessary for complete non-invasive radiation dose planning in the treatment of malignant melanoma both for NCT as well as other therapeutic modalities.

Topics: Boron; Boron Compounds; Brain; Brain Neoplasms; Fluorine Radioisotopes; Humans; Isotopes; Lymphatic Metastasis; Melanoma; Phenylalanine; Tomography, Emission-Computed