Systemic targeted alpha radiotherapy for cancer.

BACKGROUND: The fundamental principles of internal targeted alpha therapy forcancer were established many decades ago.The high linear energy transfer (LET) ofalpha radiation to the targeted cancer cellscauses double strand breaks in DNA. Atthe same time, the short range radiation spares adjacent normal tissues. This targeted approach complements conventional external beam radiotherapy and chemotherapy. Such therapies fail on several fronts, such as lack of control of some primary cancers (e.g. glioblastoma multiforme) and to inhibit the development of lethal metastaticcancer after successful treatment of the primary cancer. OBJECTIVE: This review charts the developing role of systemic high LET, internalradiation therapy. METHOD: Targeted alpha therapy is a rapidly advancing experimental therapy thatholds promise to deliver high cytotoxicity to targeted cancer cells. Initially thoughtto be indicated for leukemia and micrometastases, there is now evidence that solidtumors can also be regressed. RESULTS: Alpha therapy may be molecular or physiological in its targeting. Alphaemitting radioisotopes such as Bi-212, Bi-213, At-211 and Ac-225 are used to labelmonoclonal antibodies or proteins that target specific cancer cells. Alternatively, Radium-233 is used for palliative therapy of breast and prostate cancers because of its bone seeking properties. CONCLUSION: Preclinical studies and clinical trials of alpha therapy are discussedfor leukemia, lymphoma, melanoma, glioblastoma multiforme, bone metastases, ovarian cancer, pancreatic cancer and other cancers.

Orthotopic administration of (213)Bi-bevacizumab inhibits progression of PC3 xenografts in the prostate.

AIM: To investigate orthotopic targeted α-radioimmunotherapy for the control of early-stage PC3 prostate cancer nude mouse xenografts using the radiolabeled bevacizumab (BZ) immunoconjugate ((213)Bi-BZ), which emits short-range α-radiation. MATERIALS & METHODS: 10(6) PC3 human prostate cancer cells were injected into the lower capsule of the mouse prostate gland 1 week prior to α-radioimmunotherapy. Mice were euthanized and assessed for tumour growth at 2 (two mice), 4 (two mice) and 6 weeks (three mice) post-therapy. The no-therapy control mice received a saline injection in equal volume to each BZ administration. RESULTS: (213)Bi-BZ is significantly more efficacious in inhibiting xenograft progression in the prostate gland compared with BZ alone (p = 0.009) and when compared with the 'no therapy' protocol (p < 0.0001). CONCLUSION: Orthotopic administration of (213)Bi-BZ greatly improves the early control of organ-confined prostate cancer compared with BZ alone (p < 0.01).

Paradigm lost: reconsidering functional form and group hypotheses in marine ecology.

Although functional form and functional group models for marine algae have been used extensively, there is little general literature support for these models, and many studies have shown that associated hypotheses are often incorrect. In functional form/group models, a wide range of ecological and physiological functions are assumed to be correlated with general algal form or morphology. In contrast, functional group approaches have been used most successfully in terrestrial and aquatic systems when groupings are based on a particular function rather than overall plant morphology, and when addressing ecosystem-level questions. In this type of functional group approach, a given set of species would likely be grouped differently depending on the function under consideration. Functional groupings are appropriate for many situations and questions, but not all. Certainly, grouping taxa by a particular function can be very useful and often necessary for many ecosystem-level questions and modeling, especially where qualitative results are more important than quantitative predictions, and when there are too many species in a system to consider them all individually. However, when one considers species-species interactions or questions about population biology, the specific responses of individual species must be considered. To make functional group models more useful, we recommend that groupings be based on specific functions (e.g. nutrient uptake rates, photosynthesis rates, herbivore resistance, disturbance resistance, etc.) rather than gross morphology. Explicit testing of performance of a particular function should be made before generalizations can be assumed, and groupings should be used for questions/approaches where they are most appropriate. If models fail when tested, they should be modified using the additional information to generate new hypotheses and models, and then retested.