Radioimmunotherapy: Clinical results and dosimetric considerations

Radiolabeled antibodies for cancer therapy are being investigated in clinical trials in more than 30 centers. ¹³¹Iodine-labeled antibody (Ab) therapy of solid tumors has produced few responses when given alone. When given in conjunction with chemotherapy and external beam therapy in hepatoma patients, objective responses have occurred. Because of the short range of ¹³¹I, ⁹⁰Y and ¹⁸⁶Re are being studied and objective responses have occurred in patients without the addition of other therapies. ¹³¹I-labeled Ab therapy of lymphoma, a radioresponsive tumor, has produced a much higher objective response rate than in other solid tumors. Regional RIT has not been shown to offer a definite advantage over the intravenous route. Tumor doses have generally been less than 2000 cGy per treatment with some tumors receiving higher doses. The bone marrow is the dose-limiting organ for RIT and marrow cryopreservation with subsequent reinfusion may prove useful.     

In vitro exposure of mammalian cells to radon: dosimetric considerations

We have developed a model to calculate the dose to the cell nucleus in cells exposed in suspension to radon and/or radon progeny. The model addresses the influence of (1) different radiation qualities and energies in the irradiation milieu; (2) the contribution to dose from radioactivity in the medium surrounding the cell after exposure to the radon gas as well as that from excess radon progeny associated with the cell; (3) the geometry of the cell and of the radiosensitive target, the cell nucleus; (4) the intracellular localization of the radionuclides; (5) attenuation of the alpha particles by the cytoplasm; (6) the radionuclide concentrations in the medium; and (7) the length of exposure. Investigation of the influence of these various parameters was made using an irradiation system in which cells were exposed to 212Bi, which decays to stability with the emission of an alpha particle (either 6.05 or 8.78 MeV). The information from these studies was then used to develop the system further for more complex systems in which 222Rn and its progeny are present. The model takes into account the contribution of dose from different radiation sources using scintillation counts of the medium and the cells, and it is useful for calculations of dose in situations where cells are exposed in suspension culture.     

Endovascular gamma-irradiation to prevent recurrent femoral in-stent restenosis. A case report

We report about a patient with twice recurrence of femoral in-stent restenoses. Centered endoluminal gamma-irradiation with 192 iridium was performed immediately after the second stent recanalization. The irradiation dose was 14 Gy calculated at 2-mm depth of vessel wall. One-year follow-up demonstrates neither clinical nor angiographic evidence of restenosis.     

Clinical trials of vascular brachytherapy for in-stent restenosis: update

Vascular brachytherapy has become the therapeutic strategy of choice for in-stent restenosis. Clinical trials evaluating the effectiveness and safety of this technology have enrolled nearly 4000 patients using both gamma and beta emitters. At present, ongoing controversies include optimal dosimetry, whether beta emitters are as effective as gamma and whether centering delivery systems perform better than non-centering systems. Complications of brachytherapy such as edge effect, late thrombosis and late restenosis have received increasing attention. This review provides an update of the current status of clinical trials utilizing vascular brachytherapy to prevent the recurrence of in-stent restenosis.     

Endovascular brachytherapy in the prevention of vascular restenosis

Purpose: To evaluate the technical feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA). Materials and methods: Ten patients with recurrence of stenosis in the femoropopliteal region underwent PTA followed by endovascular irradiation with Iridium-192 a high-dose rate after-loading technique. We used a single fraction of dose 12 Gy given in 3 mm from the source axis in the stenotic vessel segment. Results: During follow-up of 59–580 days restenosis occurred in four patients 111, 460, 472 and 580 days after irradiation. All other patients are without restenosis. No radiation-associated side effects were observed. Conclusions: Endovascular brachytherapy of restenosis in the femoropopliteal region is technically feasible, and may be done as a part of the PTA. These encouraging results open the possibility of reduction of restenosis by the present method.     

Ice as a water-equivalent solid medium for brachytherapy dosimetric measurements

Precise positioning of source and dosimeters is essential in the experimental determination of dosimetric characteristics of brachytherapy sources. Various near-water equivalent solid phantoms have been used to achieve the necessary precision in the positioning. However, the uncertainties in their chemical compositions may lead to non-negligible uncertainties in the determined doses. It is proposed here that ice may be used as an alternative to the conventional solid phantoms, since its chemical composition is identical to water while the positioning advantage associated with solid phantoms is retained. In this work, the feasibility of using ice as a solid phantom for brachytherapy dosimetry is investigated. Ice-to-water conversion factors are calculated at distances of 0.2–10 cm from the source, for six high- and low-energy photon-emitting brachytherapy sources and mono-energetic photons between 10 keV to 2.0 MeV. Practical issues and challenges associated with measuring dose in an ice phantom are discussed.     

End-to-end dosimetric audit: A novel procedure developed for Irish HDR brachytherapy centres

PurposeA dosimetric audit of Ir-192 high dose rate (HDR) brachytherapy remote after-loading units was carried out in 2019. All six brachytherapy departments on the island of Ireland participated in an end-to-end test and in a review of local HDR dosimetry procedures.Materials and methodsA 3D-printed customised phantom was created to position the following detectors at known distances from the HDR source: a Farmer ionization chamber, GafChromic film and thermoluminescent dosimeters (TLDs). Dedicated HDR applicator needles were used to position an Ir-192 source at 2 cm distance from these detectors. The end-to-end dosimetry audit pathway was performed at each host site and included the stages of imaging, applicator reconstruction, treatment planning and delivery. Deviations between planned and measured dose distributions were quantified using gamma analysis methods. Local procedures were also discussed between auditors and hosts.ResultsThe mean difference between Reference Air Kerma Rate (RAKR) measured during the audit and RAKR specified by the vendor source certificate was 1.3%. The results of end-to-end tests showed a mean difference between calculated and measured dose of 2.5% with TLDs and less than 0.5% with Farmer chamber measurements. GafChromic films showed a mean gamma passing rates of >95% for plastic and metal applicators with 2%/1 mm global tolerance criteria.ConclusionsThe results of this audit indicate dosimetric consistency between centres. The ‘end to end’ dosimetry audit methodology for HDR brachytherapy has been successfully implemented in a multicentre environment, which included different models of Ir-192 sources and different treatment planning systems.The ability to create a 3D-printed water-equivalent phantom customised to accurately position all three detector types simultaneously at controlled distances from the Ir-192 source under evaluation gives good reproducibility for end-to-end methodology.     

Review of endovascular brachytherapy physics for prevention of restenosis

Intraluminal irradiation of coronary and peripheral arteries has been shown to reduce neointimal hyperplasia following balloon angioplasty, thereby inhibiting restenosis. Several irradiation techniques are being investigated, including temporary intravascular insertion of high activity gamma- or beta-emitting seeds and wires; inflation of dilatation balloon catheter with radioactive liquid or gas; insertion of miniature x-ray tubes via coronary catheters; permanent implantation of radioactive stents; and postangioplasty fractionated external beam irradiation. Unlike conventional brachytherapy, intravascular treatment of restenosis requires accurate knowledge of dose at distances of 0.5-5 mm from the radioactive source. This requirement presents special problems with regard to source calibration and dose specification, because dose gradients at such close distances from a radioactive source are extremely large. This makes it virtually impossible to define the characteristics of an ideal radiation source without some knowledge of the location and radiosensitivity of the target tissues, plus the radiotolerance of normal tissues. Hence, the current debate over whether beta or gamma sources are to be preferred. Imprecise knowledge of dose-volume effects for coronary arteries, plus uncertainties in the biological time sequencing of restenosis fuel a second debate on whether external beam treatments may be efficacious, and whether or not permanent radioactive stents may prove superior to high dose, single fraction brachytherapy. We review here the dosimetric properties of the various irradiation techniques and isotopes that have been proposed, including aspects of radiation safety, dose homogeneity, and practical aspects of source delivery.