Selecting an intervention time for intravascular enzymatic cleavage of peptide linkers to clear radioisotope from normal tissues.

Unlabelled: Protease degradable linkers have been proposed to improve the therapeutic index (TI) (i.e., tumor to normal tissue) of molecular targeted radioisotope therapy by reducing unbound radiotargeting agent in the blood and other normal tissues.

Dosimetry for quantitative analysis of the effects of low-dose ionizing radiation in radiation therapy patients.

We have developed and validated a practical approach to identifying the location on the skin surface that will receive a prespecified biopsy dose (ranging down to 1 cGy) in support of in vivo biological dosimetry in humans. This represents a significant technical challenge since the sites lie on the patient's surface outside the radiation fields. The PEREGRINE Monte Carlo simulation system was used to model radiation dose delivery, and TLDs were used for validation on phantoms and for confirmation during patient treatment.

Planning time for peripheral blood stem cell infusion after high-dose targeted radionuclide therapy using dosimetry.

Unlabelled: Myelotoxicity can be ameliorated by peripheral blood stem cell (PBSC) infusion. Continuous irradiation by radioactivity retained in the body after high-dose radioimmunotherapy can damage PBSCs if they are transfused too early. Previously, infusion time was predetermined using the radioactivity concentration in the blood.

Radiation phantom with humanoid shape and adjustable thickness (RPHAT).

A new radiation phantom with humanoid shape and adjustable thickness (RPHAT) has been developed. Unlike the RANDO phantom which is a fixed thickness, this newly designed phantom has adjustable thickness to address the range of thicknesses of real-world patients. RPHAT allows adjustment of the body thickness by being sliced in the coronal (instead of axial) direction.

Film dosimetry in the peripheral region using multiple sensitometric curves.

We present a method for applying film dosimetry to the peripheral region utilizing multiple sensitometric curves. There are many instances when the dose to the peripheral region outside the field edges is of clinical and/or research interest. Published peripheral dose data may be insufficient if detailed dose modeling is required, and in those cases measurements must be performed.

Enhanced therapeutic index of radioimmunotherapy (RIT) in prostate cancer patients: comparison of radiation dosimetry for 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-peptide versus 2IT-DOTA monoclonal antibody linkage for RIT.

Purpose: Radioimmunotherapy delivered by radiometal immunoconjugates and followed by marrow support is dose limited by deposition of radioactivity in normal organs. To increase elimination of radioactivity from the liver and body and, thus, minimize hepatic radiation dose, a peptide having a specific cathepsin B cleavage site was placed between the radiometal chelate DOTA (1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid) and the monoclonal antibody m170, and the comparative pharmacokinetics was evaluated in prostate cancer patients.

Experimental Design: (111)In-DOTA-2IT-m170 and (111)In-DOTA-peptide-(GGGF)-m170, representing the same monoclonal antibody and chelate with and without the cleavable linkage, were studied in comparable groups of prostate cancer patients (17 with In-2IT-BAD-m170 and 8 with In-DOTA-peptide-m170).

Treatment planning for molecular targeted radionuclide therapy.

Molecular targeted radionuclide therapy promises to expand the usefulness of radiation to successfully treat widespread cancer. The unique properties of radioactive tags make it possible to plan treatments by predicting the radiation absorbed dose to both tumors and normal organs, using a pre-treatment test dose of radiopharmaceutical. This requires a combination of quantitative, high-resolution, radiation-detection hardware and computerized dose-estimation software, and would ideally include biological dose-response data in order to translate radiation absorbed dose into biological effects.

Radiation dosimetry for radionuclide therapy in a nonmyeloablative strategy.

Radionuclide therapy extends the usefulness of radiation from localized disease of multifocal disease by combining radionuclides with disease-seeking drugs, such as antibodies or custom-designed synthetic agents. Like conventional radiotherapy, the effectiveness of targeted radionuclides is ultimately limited by the amount of undesired radiation given to a critical, dose-limiting normal tissue, most often the bone marrow. Because radionuclide therapy relies on biological delivery of radiation, its optimization and characterization are necessarily different than for conventional radiation therapy.

The impact of electron transport on the accuracy of computed dose.

The aim of this work was to investigate the accuracy of dose predicted by a Batho power law correction, and two models which account for electron range: A superposition/convolution algorithm and a Monte Carlo algorithm. The results of these models were compared in phantoms with cavities and low-density inhomogeneities. An idealized geometry was considered with inhomogeneities represented by regions of air and lung equivalent material.

A source model for efficient brachytherapy computations with Monte Carlo.

Monte Carlo techniques have the potential for producing accurate brachytherapy dose distributions in heterogeneous finite geometries. However, for routine clinical use, computational speed must be adequate. A fast, all-particle, CT-based Monte Carlo code called PEREGRINE is being developed at Lawrence Livermore National Laboratory for radiation treatment planning.