[Results of combined radiotherapy of choroid melanomas]. / Rezul'taty sochetannoi luchevoi terapii khorioidal'nykh melanom.

Method of combined radiotherapy of choroid melanomas, proposed by the authors, includes transscleral irradiation of the tumor by rutenium ophthalmoapplicators and simultaneous intracorporeal irradiation with 59Fe. Twenty-seven patients were treated. Morphological examination of enucleated eyes showed the capacity of 57Fe to incorporate in tumor cell, and observations indicate that this method of treatment not only extends the indications for organ-sparing radiotherapy of uveal melanomas, but delays the development of distant metastases as well.

Positron emission tomography and radioimmunotargeting--general aspects.

To optimize radioimmunotherapy, in vivo information on individual patients, such as radionuclide uptake, kinetics, metabolic patterns and optimal administration methods, is important. An overriding problem is to determine accurately the absorbed dose in the target organ as well as critical organs. Positron Emission Tomography (PET) is a superior technique to quantify regional kinetics in vivo with a spatial resolution better than 1 cm3 and a temporal resolution better than 10 s. However, target molecules often have distribution times of several hours to days. Conventional PET nuclides are not applicable and alternative positron-emitting nuclides with matching half-lives and with suitable labelling properties are thus necessary. Over many years we have systematically developed convenient production methods and labelling techniques of suitable positron nuclides, such as 110In(T(1/2) = 1.15 h), 86Y(T(1/2) = 14 h), 76Br(T(1/2) = 16 h) and 124I(T(1/2) = 4 days). 'Dose planning' can be done, for example, with 86Y- or 124I-labelled ligands before therapy, and 90Y- and 131I-labelled analogues and double-labelling, e.g. with a 86Y/90Y-labelled ligand, can be used to determine the true radioactivity integral from a pure beta-emitting nuclide. The usefulness of these techniques was demonstrated in animal and patient studies by halogen-labelled MAbs and EGF-dextran conjugates and peptides chelated with metal ions.

[Combined radiotherapy of uveal melanoma]. / Sochetannaia luchevaia terapiia uvealnykh melanom.

Fifteen patients with uveal melanoma were exposed to combined radiotherapy: transscleral exposure of melanoma using a ruthenium ophthalmoapplicator and intracorporeal administration of 59Fe. Radiation reaction of the tumor was potentiated by combined exposure.

Additional myeloablation with 52Fe before bone marrow transplantation.

For many hematological malignancies, high-dose chemoradiotherapy followed by bone marrow transplantation offers the best and sometimes the only chance for cure. However, the main causes of failure of this therapy are relapse and toxicity. In order to selectively deliver higher doses of radiotherapy to the bone marrow and to spare normal organs, we explored 52Fe therapy before a conventional BMT conditioning regimen. Twenty-four patients at high risk for relapse after BMT were included in a phase II study. The median follow-up was 42 months. The median 52Fe dose was 59 mCi. This resulted in a median radiation-absorbed dose (RAD) to the BM of 626 rad. The median RAD to the liver was 338 rad. No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The 3-year DFS probability was 49% (95% CI: 20-78%). Eight patients have relapsed, three of them in extramedullary sites. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before bone marrow transplantation without excessive toxicity.

52Fe for additional marrow ablation before bone marrow transplantation.

The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation-absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.

In vivo stability of ferric hydroxide macroaggregates (FHMA). Is it a suitable carrier for radionuclides used in synovectomy?

Ferric hydroxide macroaggregates (FHMA) have been widely used as a carrier for several radionuclides used in radiation synovectomy. Different rates of extra-articular leakage of radioactivity have been observed with 90Y and 165Dy. In order to understand the mechanism(s) involved in the extra-articular leakage of radioactivity, the in vivo stability of FHMA carrier was studied. Following an injection of [59Fe]Fe-FHMA into the knees of normal rabbits, the cumulative leakage of [59Fe]Fe-FHMA was 2.9% at 5 days and 12.3% at 14 days. More than 60% of this activity was in the blood. But when FHMA was double labeled with 59Fe and 166Ho, the 59Fe leakage significantly increased to 18.5% at 5 days and 27% by 14 days. The instability of FHMA is accelerated when it is complexed with 166Ho and may be due to the "mass effect" of 166Ho or due to radiolysis induced by high energy beta particles from 166Ho. These results suggest that FHMA is a suitable carrier only for the short lived radionuclides used in synovectomy.

A novel cancer therapy using a Mössbauer-isotope compound.

Cancer radiotherapy uses high doses of ionizing radiation (1-10(2) Gy; 10(2)-10(4) rad) because only a small fraction of the absorbed dose leads to lethal double-strand breaks in DNA. These breaks are more efficiently produced by Auger electrons (1-10 eV nm-1) generated in proximity to the DNA. The energy of these electrons (on average 21 electrons for the decay of 125I) is dissipated within 10-100 nm of the Auger event and produces multiple double-strand DNA breaks. A single Auger event can be lethal to a cell and is comparable to more than 10(5) photon absorption events in conventional radiotherapy. We now report that 57Fe(III).bleomycin, administered to malignant cells in vitro and in vivo and irradiated with resonant Mössbauer gamma rays (14.4 keV), causes ablation of the malignant cells, presumably by Auger cascade, with extremely small radiation doses--about 10(-5) Gy. As a basis for comparison, about 5 Gy is necessary to achieve a similar effect with conventional radiotherapy.