Recent advances in radionuclide therapy

A Bridge not too Far: Personalized Medicine with the use of Theragnostic Radiopharmaceuticals

“…Over 2 decades ago, when Y-90 began to be promoted for radioimmunotherapy and was undergoing rapid development, it was considered necessary to use In-111-monoclonal antibody (mAb) as a surrogate to carry out biodistribution and imaging studies in order to predict the dosimetry and toxicity prior to doing the therapy with Y-90-mAb, because of the lack of imageable photons in Y-90 emissions. After some very careful studies, the Julich group 5 and our own group at Brookhaven 6,7 showed that at best, it was hazardous to do so because these were two different elements whose biochemistry had many similarities but also many striking dissimilarities as well. Interestingly, this practice still continues, because of the lack of an alternate solution.…”

The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m

“…However, low-energy beta emitters may be equally or more effective in reducing inflammation for small to medium joints since a much larger radiation dose could be delivered to the synovium without excessive irradiation of surrounding tissue (Srivastava, 1996c). This could be analogous to the effectiveness of the short-range conversion electrons from Sn-117m for bone pain palliation, compared to the high-energy beta emitter Sr-89 (Srivastava, 1996c;Srivastava and Dadachova, 2001). The only clinical example to date for treating synovial inflammation using a low-energy beta emitter is the use of colloids of Er-169 (avg.…”

Antibody-targeted radiation cancer therapy

“…Other clinically relevant β --emitters include 90 Y, 67 Cu, 186 Re and, more recently, 177 Lu, with others having either been investigated or proposed (see below). Discussion of these will be limited here, except to state that emission energy and half-life requirements can be met with a small cross-section of isotopes that are already available 5 . Direct radio-iodination occurring with extant tyrosine moieties of the protein has dominated this field.…”

“…With the elimination of many obstacles and a better understanding of the inherent limitations of mAbs, coupled with interest and support from industry, several radiolabelled mAbs have been, or are now being evaluated in Phase III clinical trials (TABLE 1). In the past two years, the US FDA has approved the use of two anti-CD20 mAb regimens involving radionuclides for the treatment of NHL: Zevalin (Biogen Idec) and Bexxar (Corixa/ GlaxoSmithKline), which are based on the radiolabelled mAbs 90 Y ibritumomab and 131 I tositumomab, respectively, making further targeted radiation therapy products probable 5 . This review describes radiolabelled-mAb-directed approaches, with an emphasis on the components (protein, radionuclide and chemistry), and discusses clinical trials of radiolabelled mAbs in haematological cancers.…”

“…A sampling of available isotopes (TABLE 2) results in several alternatives comprising three types of emission: β --particles, α-particles and Auger electrons 5 (FIG. 2).…”