Search

Molecular imaging and therapy is based on a radiolabeled molecule that binds to a unique feature of a cell. Prostate Specific Membrane Antigen [PSMA] is a complex antigen with an extra-cellular, transmembrane and intra-cellular component that is uniquely expressed on prostate tissue and has a greater degree of expression on prostate carcinoma. The degree of PSMA expression increases with the degree of aggressiveness of the prostate carcinoma. A murine monoclonal antibody [termed J591] has been developed that binds to the extra-cellular epitope of PSMA with a high degree of affinity and specificity. It has been “humanized” and radiolabeled with the radionuclides Indium-111 [useful for imaging], Yttrium-90 [a radiometal that emits a beta particle which is potentially useful for targeted radionuclide therapy], and Lutetium-177 [which also emits a beta particle that is useful for targeted therapy as well as a gamma photon that can be imaged]. Over several years, physicians and scientists in nuclear medicine, urology and medical oncology have evaluated radiolabeled forms of hJ591 for therapy. In general, serum PSA has been used as evidence of recurrent and progressive disease in men with proven prostate carcinoma. The Maximum Tolerated Dose [MTD] for a single administration has been identified as 2.6 GBq (70 mCi)/m2. At this dose, PSA responses have been seen in many patients. The response is very dose-dependant with fewer responses observed at 2.25 GBq/m2. Accordingly, a dose fractionation protocol has been evaluated in which patients receive 2 doses, 2 weeks apart. The MTD for the fractionated protocol is 1.5 GBq/ m2 for a total dose of 3.0 GBq/ m2. Initial studies were performed in patients with advanced metastatic disease. More recently, additional protocols 1) to evaluate the potential efficacy of this therapy in patients with initial evidence of biochemical failure (i.e. rising PSA after initial therapy) and 2) to evaluate the incremental value of radiolabeled J591 as a supplement to Docetaxel chemotherapy.

Radiolabeled monoclonal antibodies for the treatment of follicular low-grade non-Hodgkin’s lymphoma have been available for several years in the United States and more recently throughout Europe. Since their introduction to treatment of refractory or relapsed patients, they have been evaluated for efficacy earlier in the course of the disease including so-called 1st line therapy in conjunction with initial chemotherapy and as consolidation therapy in patients who have achieved remission following a course of chemotherapy. It can be expected that these agents will become more widely available. Two agents are currently distributed commercially: Bexxar® consisting of 131I-labeled tositumomab and cold (unlabeled) tositumomab and Zevalin® consisting of 90Y-labeled Ibritumomab and cold rituximab. All 3 antibodies recognize a cell surface antigen, CD20, found on normal and malignant B lymphocytes characteristic of follicular lymphoma. The nomenclature: ”…tumomab” indicates that it is a tumor murine monoclonal antibody while “…ximab” indicates that it is a chimeric molecule in which a portion of the murine IgG has been removed and replaced with an equivalent component of human IgG. Rituximab is available in many countries for use as an immunotherapeutic either alone in relapsed patients or in conjunction with standard chemotherapeutic regimen. Because of the limited access to the radiolabeled products in Australia, Harvey Turner and colleagues in Perth radioiodinated rituxan (the nonradioactive component of Zevalin®), developed a protocol similar to Bexxar® and obtained gratifyingly similar good results. Clinical use depends upon evidence of CD20 expression (usually available from biopsy material at diagnosis), confirmation of less than 25% of marrow involvement, platelet counts >100,000 and preferably 150,000 and granulocyte count > 3500. For either product, dosing is based on platelet count and body weight [up to 137% ideal weight). Zevalin® dosage is 15 MBq (0.4 mCi)/kg if platelets exceed 150K; 11 MBq (0.3 mCi)/kg between 100K-150K. Bexxar® administration is based on whole body radiation absorbed dose determined by measuring whole body counts on 3 occasions after administration of 185 MBq (5 mCi) of the 131I-tositumomab. In all instances, cold antibody is infused prior to the labeled component. In early studies, 67-80% of the patients achieved a partial or complete response of greater duration than in their prior treatment. More recently, when used as the 1st line or consolidation therapy, near 100% overall response rates have been observed.

18F-FDG PET/CT has become essential in the management of patients with Hodgkin’s and non-Hodgkin’s lymphoma. The utility of 18F-FDG PET/CT imaging is based upon increased anaerobic metabolism of neoplastic tissue. The degree of hypermetabolism is somewhat proportional to lymphoma grade. Based on the ability of 18F-FDG PET/CT to identify hypermetabolic tissue, it has greater sensitivity and specificity for the detection of tumors in general and lymphoma in particular compared to CT or MRI. 18FFDG PET/CT has made a significant impact in lymphoma management in the following instances: 1. Extent of disease in patients already diagnosed with lymphoma; 2. Identification of hypermetabolic disease in lymphadenopathy identified by other means; 3. Evaluation of response to therapy - with greater specificity than CT alone; 4. Early detection of recurrent disease; 5. Identification of transformation from low grade to high-grade lymphoma; 6. Prediction of response to therapy and prognosis. In many clinical trials, 18F-FDG PET/CT has replaced CT as the standard for assessment of residual disease. It has become a standard procedure at the time of initial diagnosis and following completion of therapy as well at 6-24 month intervals during the follow-up or upon the recurrence of symptoms suggestive of relapse. On an investigational basis, we have demonstrated that resolution of lymph node hypermetabolism, as early as following a single cycle of chemotherapy, is predictive of a prolonged disease-free interval whereas failure to respond after a single cycle indicates that even if there is resolution of disease after completion of a full course of treatment, relapse occurs earlier. If confirmed by additional studies, early 18F-FDG PET/CT evaluation of response may provide a basis to select patients for a change to more aggressive or alternate therapy. In fact, it may also identify a sub-population of patients who do not require an extended course of chemotherapy.

We used diffusion tensor imaging (DTI) to study 2 patients with traumatic brain injury. The first patient recovered reliable expressive language after 19 years in a minimally conscious state (MCS); [...]