Calcitonin DT may be superior to initial clinical staging and among the most powerful prognostic indicators in MTC.

In lymphoid malignancies and in certain solid cancers such as medullary thyroid carcinoma, somewhat mixed success has been achieved when applying radioimmunotherapy (RIT) with beta-emitters for the treatment of refractory cases. The development of novel RIT with alpha-emitters has created new opportunities and theoretical advantages due to the high linear energy transfer (LET) and the short path length in biological tissue of alpha-particles. These physical properties offer the prospect of achieving selective tumoural cell killing. Thus, RIT with alpha-emitters appears particularly suited for the elimination of circulating single cells or cell clusters or for the treatment of micrometastases at an early stage. However, to avoid non-specific irradiation of healthy tissues, it is necessary to identify accessible tumoural targets easily and rapidly. For this purpose, a small number of alpha-emitters have been investigated, among which only a few have been used for in vivo preclinical studies. Another problem is the availability and cost of these radionuclides; for instance, the low cost and the development of a reliable actinium-225/bismuth-213 generator were probably determining elements in the choice of bismuth-213 in the only human trial of RIT with an alpha-emitter. This article reviews the literature concerning monoclonal antibodies radiolabelled with alpha-emitters that have been developed for possible RIT in cancer patients. The principal radio-immunoconjugates are considered, starting with physical and chemical properties of alpha-emitters, their mode of production, the possibilities and difficulties of labelling, in vitro studies and finally, when available, in vivo preclinical and clinical studies.

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pRAIT against CEA induced long-term disease stabilization and a significantly longer survival in high-risk patients with Ct DTs less than 2 years, compared with similarly high-risk, untreated patients. Ct DT and bone-marrow involvement appear to be prognostic indicators in MTC patients who undergo pRAIT.

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We calculated the mean absorbed fractions, specific absorbed fractions and mean doses per unit of cumulated activity in source spheres 10 microm-2 cm in radius for 22 beta-emitting radionuclides potentially useful in radioimmunotherapy. We considered two models of radionuclide distribution, either uniform at the surface of the source or throughout its volume. For each model, we calculated both the absorbed fractions in the spherical segments composing the source and the mean absorbed fractions. For surface distribution, we calculated the mean dose per unit of cumulated activity for a concentric sphere with a small radius (5 microm) in order to determine the minimal dose delivered to the target. Calculations were performed using point kernels for monoenergetic emissions and then integrated into the beta spectra of the different emitters (32p, 33p, 47Sc, 67Cu, 77As, 90Y, 105Rh, 109Pd, 111Ag, 121Sn, 131I, 142Pr, 143Pr, 149Pm, 153Sm, 159Gd, 166Ho, 177Lu, 186Re, 188Re, 194Ir and 199Au). Monoenergetic emissions were taken into account. Results are reported in the form of tables to facilitate use during dosimetric studies for radioimmunotherapy. An application is presented showing the potential utility of associating emitters with different energies in order to sterilize a range of tumour targets of variable size.

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Radiolabeled antibodies were studied first for tumor detection by single-photon imaging, but FDG PET stopped these developments. In the meantime, radiolabeled antibodies were shown to be effective in the treatment of lymphoma. Radiolabeling techniques are well established and radiolabeled antibodies are a clinical and commercial reality that deserves further studies to advance their application in earlier phase of the diseases and to test combination and adjuvant therapies including radiolabeled antibodies in hematological diseases. In solid tumors, more resistant to radiations and less accessible to large molecules such as antibodies, clinical efficacy remains limited. However, radiolabeled antibodies used in minimal or small-size metastatic disease have shown promising clinical efficacy. In the adjuvant setting, ongoing clinical trials show impressive increase in survival in otherwise unmanageable tumors. New technologies are being developed over the years: recombinant antibodies and pretargeting approaches have shown potential in increasing the therapeutic index of radiolabeled antibodies. In several cases, clinical trials have confirmed preclinical studies. Finally, new radionuclides, such as lutetium-177, with better physical properties will further improve the safety of radioimmunotherapy. Alpha particle and Auger electron emitters offer the theoretical possibility to kill isolated tumor cells and microscopic clusters of tumor cells, opening the perspective of killing the last tumor cell, which is the ultimate challenge in cancer therapy. Preliminary preclinical and preliminary clinical results confirm the feasibility of this approach.