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Radioactive iodine therapy has evolved over the past 70 years from treatment of known metastatic thyroid carcinoma to include adjuvant use to decrease the incidence of recurrent disease and to ablation of normal remnant tissue following thyroidectomy, even for minimal tumor involvement. Advances in laboratory testing, development of drugs useful in radioiodine treatment, as well as advances in radiation detection and imaging instrumentation, have progressively improved the utility of radioiodine therapy of differentiated thyroid carcinoma. Guidelines have proliferated and they have become more detailed and complex. This trend is likely to continue as the science and technology involved increases in sophistication and efficacy. [ABSTRACT FROM AUTHOR]

Abstract. Positron emission tomography (PET) imaging has become a very useful technique for staging and monitoring therapy response in lymphoma, providing unique information about the biological behavior of disease. Increased fluorine-18 fluorodeoxyglucose (FDG) uptake in lymphoma is based on elevated glycolysis and longer residence time of FDG in malignant cells compared with most normal tissues. The metabolic information provided by this technique suggests that FDG-PET may be more sensitive than the anatomical imaging modalities. Computed tomography (CT) is the principal imaging modality for the staging and restaging of lymphoma. Nonetheless, this technique has significant shortcomings, particularly in the post-therapy setting. Gallium-67 scintigraphy has played an important role in monitoring response to therapy and follow-up of patients; however, the sensitivity of [sup 67]Ga depends on the subtype of lymphoma and the size and location of disease. Published results strongly indicate that FDG-PET is superior to [sup 67]Ga imaging and may be equal or superior to CT for the detection of nodal as well as extranodal involvement in lymphoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 18F-FDG 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: The role of the base in the synthesis of 3′-deoxy-3′-[18F]fluorothymidine, [18F]FLT, via nucleophilic substitution of the nosyl group with [18F]fluoride was investigated. The rate of 18F-incorporation into the molecule dramatically changed as a function of the precursor-to-base ratio. In the presence of excess base, the precursor was consumed by elimination before substitution was complete. When the precursor-to-base ratio was optimal, an overall [18F]FLT yield of 30–40% was achieved even if the precursor amount was as small as 8–13mg. [Copyright &y& Elsevier]

Radioimmunotherapy (RIT) is a promising new treatment option for patients with relapsed/refractory non-Hodgkin's lymphoma. Clinical trials have demonstrated that both iodine-131 ([SUP131]I) and yttrium-90 ([SUP90]Y) are suitable radionuclides for RIT. Iodine-131 and [SUP90]Y differ markedly in their physical properties including half-life, path length, type of energy emissions, intracellular stability, and the organs targeted by the free radionuclide. Both radionuclides can be safely administered in the outpatient setting under current Nuclear Regulatory Commission guidelines. Potential advantages of [SUP131]I for RIT include availability, stable chemistry, longer half-life, and an emission spectrum that allows for dosimetric studies and therapy with the same immunoconjugate. By contrast, [SUP90]Y has a longer path length and superior intracellular stability compared with [SUP131]I. Yttrium-90 may therefore be preferable to [SUP131]I for patients with bulky disease, poorly vascularized solid tumors, or when targeting internalized antigens. Although [SUP90]Y emits no gamma photon, dosimetry studies for [SUP90]Y RIT can be performed using a surrogate radionuclide such as indium-111. Both [SUP131]I- and [SUP90]Y-labeled anti-CD20 antibodies have demonstrated efficacy in treating relapsed/refractory non-Hodgkin's lymphoma. Further studies are needed, however, to determine if the differences in the pharmacology of [SUP131]I and [SUP90]Y are clinically relevant. [ABSTRACT FROM AUTHOR]

Study Objective: To image and identify by noninvasive methods the sites of low-density lipoprotein (LDL) catabolism in patients with myeloproliferative disease in whom chronic hypocholesterolemia was previously reported.Study Design: The 99mTechnetium-LDL (Tc-LDL) distribution in patients with myeloproliferative diseases was compared with that in normal subjects. The Tc-LDL distribution was also compared with the distribution and organ uptake of a macrophage-seeking radiotracer. 99mTc-sulfur colloid (Tc-SC).Setting: Major metropolitan referral center and institutional practice.Patients: Three normal subjects, two patients with polycythemia vera, two with post polycythemia myeloid metaplasia, and one with agnogenic myeloid metaplasia. The patients were being managed with hydroxyurea or phlebotomy.Intervention: Ten mCi of Tc-LDL (homologous) was injected intravenously.Measurements and Main Results: Gamma camera images of Tc-LDL biodistribution and organ uptake were obtained 4 hours after injection of the tracer. In normal subjects, the Tc-LDL was predominantly taken up by the liver, with relative nonvisualization of spleen and central or peripheral marrow. Patients with myeloproliferative disease showed marked splenic uptake of Tc-LDL. Peripheral bone marrow uptake extended to the lower tibia in two patients with post-polycythemia myeloid metaplasia. Splenic and bone marrow uptake paralleled that of Tc-SC. Hypercellularity of central and peripheral marrow at the sites of Tc-LDL uptake was confirmed by biopsy specimens. The Tc-LDL uptake, however, was not correlated with collagen fibrosis.Conclusions: These results indicate that spleen and bone marrow are sites of LDL catabolism in patients with myeloproliferative disease and suggest the role of macrophages in the hypocholesterolemia and accelerated LDL catabolism of myeloproliferative disease. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is radiosensitive. Prostate-specific membrane antigen (PSMA) is selectively overexpressed on advanced, castration-resistant tumors. Lutetium-177-labeled anti-PSMA monoclonal antibody J591 (177 Lu-J591) targets prostate cancer with efficacy and dose-response/toxicity data when delivered as a single dose. Dose fractionation may allow higher doses to be administered safely.Method: Men with metastatic castration-resistant prostate cancer refractory to or refusing standard treatment options with normal neutrophil and platelet counts were enrolled in initial phase 1b dose-escalation cohorts followed by phase 2a cohorts treated at recommended phase 2 doses (RP2Ds) comprising 2 fractionated doses of 177 Lu-J591 2 weeks apart. 177 Lu-J591 imaging was performed after treatment, but no selection for PSMA expression was performed before enrollment. Phase 2 patients had circulating tumor cell (CTC) counts assessed before and after treatment.Results: Forty-nine men received fractionated doses of 177 Lu-J591 ranging from 20 to 45 mCi/m2 ×2 two weeks apart. The dose-limiting toxicity in phase 1 was neutropenia. The RP2Ds were 40 mCi/m2 and 45 mCi/m2 ×2. At the highest RP2D (45 mCi/m2 ×2), 35.3% of patients had reversible grade 4 neutropenia, and 58.8% of patients had thrombocytopenia. This dose showed a greater decrease in prostate-specific antigen (PSA) levels and longer survival (87.5% with any PSA decrease, 58.8% with >30% decrease, 29.4% with >50% decrease; median survival, 42.3 months [95% confidence interval, 19.9-64.7]). Fourteen of 17 (82%) patients with detectable CTCs experienced a decrease in CTC count. Overall, 79.6% of patients had positive PSMA imaging; those with less intense PSMA imaging tended to have poorer responses.Conclusion: Fractionated administration of 177 Lu-J591 allowed higher cumulative radiation dosing. The frequency and depth of PSA decrease, overall survival, and toxicity (dose-limiting myelosuppression) increased with higher doses. [ABSTRACT FROM AUTHOR]

Milatuzumab (hLL1), a humanized anti-CD74 monoclonal antibody, has activity in preclinical non-Hodgkin lymphoma (NHL) models. We conducted a phase 1 trial in previously treated B-cell malignancies. Dose escalation included four planned dose levels (1.5, 4, 6 and 8 mg/kg) with milatuzumab given twice weekly for 6 weeks. After dose level 1, the schedule was changed to daily (Monday–Friday) for 10 days. Twenty-two patients were treated. The most common possibly related toxicities were infusion reaction, anemia, lymphopenia, neutropenia and thrombocytopenia. Three patients experienced dose-limiting toxicity (neutropenia, neutropenia, rash) at dose levels 1, 2 and 4, respectively. Eight patients had stable disease, with no objective responses. The serum half-life of milatuzumab was ∼2 h. In seven patients, In-111 imaging showed no clear evidence of tumor targeting. The short half-life may reflect CD74 rapid internalization and presence on extratumoral tissues; this antigen sink must be overcome to capitalize on the promising preclinical activity of the drug. [ABSTRACT FROM AUTHOR]

We prospectively evaluated the accuracy of the 2007 World Health Organization (WHO) criteria for diagnosing polycythemia vera (PV), especially in "early-stage" patients. A total of 28 of 30 patients were diagnosed as PV owing to an elevated Cr-51 red cell mass (RCM), JAK2 positivity, and at least 1 minor criterion. A total of 18 PV patients did not meet the WHO criterion for an increased hemoglobin value and 8 did not meet the WHO criterion for an increased hematocrit value. Bone marrow morphology was very valuable for diagnosis. Low serum erythropoietin (EPO) values were specific for PV, but normal EPO values were found at presentation (20%). We recommend revision of the WHO criteria, especially to distinguish early-stage PV from essential thrombocythemia. Major criteria remain JAK2 positivity and increased red cell volume, but Cr-51 RCM is mandatory for patients who do not meet the defined elevated hemoglobin or hematocrit value (>18.5 g/dL and 60% in men and >16.5 g/dL and 56% in women, respectively). Minor criteria remain bone marrow histology or a low serum EPO value. For patients with a normal EPO value, marrow examination is mandatory for diagnostic confirmation. Because the therapies for myeloproliferative disorders differ, our data have major clinical implications [ABSTRACT FROM AUTHOR]

Abstract: This study examines the relationship between fibrillar beta-amyloid (Aβ) deposition and reduced glucose metabolism, a proxy for neuronal dysfunction, in cognitively normal (NL) individuals with a parent affected by late-onset Alzheimer''s disease (AD). Forty-seven 40–80-year-old NL received positron emission tomography (PET) with 11C-Pittsburgh compound B (PiB) and 18F-fluoro-2-deoxy-d-glucose (FDG). These included 19 NL with a maternal history (MH), 12 NL with a paternal history (PH), and 16 NL with negative family history of AD (NH). Automated regions of interest, statistical parametric mapping, voxel-wise intermodality correlations, and logistic regressions were used to examine cerebral-to-cerebellar PiB and FDG standardized uptake value ratios across groups. The MH group showed higher PiB retention and lower metabolism in AD regions compared with NH and PH, which were negatively correlated in posterior cingulate, frontal, and parieto-temporal regions (Pearson r ≤ −0.57, p ≤ 0.05). No correlations were observed in NH and PH. The combination of Aβ deposition and metabolism yielded accuracy ≥ 69% for MH vs. NH and ≥ 71% for MH vs. PH, with relative risk = 1.9–5.1 (p values < 0.005). NL individuals with AD-affected mothers show co-occurring Aβ increases and hypometabolism in AD-vulnerable regions, suggesting an increased risk for AD. [Copyright &y& Elsevier]

BACKGROUND: It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS: Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2-4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS: Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at the higher radioimmunotherapy doses. CONCLUSIONS: Fractionated radioimmunotherapy with 90Y-hPAM4 and low-dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Despite recent advances, advanced prostate cancer is suboptimally responsive to current chemotherapeutic agents. Radiolabeled monoclonal antibody therapy that targets prostate-specific membrane antigen (PSMA) shows promise and is an area of active investigation. J591 is a deimmunized IgG monoclonal antibody developed to target the extracellular domain of PSMA. Preclinical and early phase clinical studies using radiolabeled J591 have demonstrated efficacy in targeting tumor cells and decreasing levels of prostate-specific antigen. Radiolabeled J591 is well-tolerated, nonimmunogenic, and can be administered in multiple doses. The dose-limiting toxicity is reversible myelosuppression with little nonhematologic toxicity. Future studies will include approaches to optimize patient selection and incorporate novel strategies to improve the success of anti-PSMA radioimmunotherapy. [ABSTRACT FROM AUTHOR]

A conference paper on the use of J591, a deimmunized immunoglobulin G (IgG) monoclonal antibody, against prostate-specific membrane antigen which is a proto-typical cell-surface marker of prostate cancer is presented. It discusses the pre-clinical and early phase clinical trials with the use of radiolabeled J591 showing efficacy in decreasing levels of prostate-specific antigen and targeting tumor cells. It adds that J591 is nonimmunogenic and effectively targets prostate cancer metastases.

Diagnostic splenectomy is frequently performed in patients with suspected or known lymphoma. We evaluated whether preoperative 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) results may correlate with splenic pathology. Of 165 patients undergoing splenectomy at the Weill Cornell Medical Centre/New York Presbyterian Hospital from 2004 to 2006, 10 were identified as being performed to evaluate known or suspected lymphoma and included a pre-splenectomy FDG-PET scan. The scans were assigned to low, intermediate or high splenic metabolic activity based on standardized uptake values (SUV). Low activity was associated with benign findings or mantle cell lymphoma at splenectomy, intermediate activity with marginal zone lymphoma and high activity with DLBCL. This comprises the largest pathologically confirmed series of cases to evaluate splenic FDG-PET uptake in suspected or known lymphoma. Low splenic SUV appears less likely to be associated with splenic involvement of lymphoma; intermediate and high values suggest presence of lymphoma. Our findings support a potential role for preoperative FDG-PET in consideration of the need for splenectomy in these settings. [ABSTRACT FROM AUTHOR]

Radioimmunotherapy (RIT) with tositumomab and iodine 131 tositumomab can produce durable and complete responses in relapsed/refractory low-grade Non-Hodgkin's lymphoma. Patients with bone marrow involvement (BMI) with tumor >25% of the intertrabecular space are generally excluded from RIT because of risk of excessive hematologic toxicity. The authors conducted a dose-escalation study of tositumomab and iodine 131 tositumomab to determine whether RIT is feasible in this population. Patients had baseline BMI of >25% and platelet count of ≥150 000/mm3. In contrast to the usual 75 cGy total body dose of radiation, dose escalation of Iodine I 131 tositumomab began at a total body dose of 45 cGy, and increased to 55 cGy in a second cohort. Dose-limiting toxicity (DLT) was defined as absolute neutrophil count <500 cells/mm3 or platelets <25 000/mm3 for >17 days, or absolute neutrophil count <750/mm3 or platelets <50 000/mm3 for >24 days. Eleven subjects were enrolled (8 at 45 cGy and 3 at 55 cGy). Estimated BMI ranged from 30 to 65% (median approximately 40%). Patients had received a median of three prior chemotherapies (range 1 – 6). One of the six evaluable patients treated at 45 cGy experienced DLT. Three patients received 55 cGy, one had hematologic DLT concurrent with lymphoma progression and extensive BMI at relapse. Three of 11 (27%) patients received hematologic supportive care. Two patients had objective responses of 1 and 42.4+ months, respectively. RIT with attenuated dose iodine 131 tositumomab for patients with >25% BMI has acceptable toxicity and can result in lymphoma responses. [ABSTRACT FROM AUTHOR]

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); the second had remained in MCS for 6 years. Comparison of white matter integrity in the patients and 20 normal subjects using histograms of apparent diffusion constants and diffusion anisotropy identified widespread altered diffusivity and decreased anisotropy in the damaged white matter. These findings remained unchanged over an 18-month interval between 2 studies in the first patient. In addition, in this patient, we identified large, bilateral regions of posterior white matter with significantly increased anisotropy that reduced over 18 months. In contrast, notable increases in anisotropy within the midline cerebellar white matter in the second study correlated with marked clinical improvements in motor functions. This finding was further correlated with an increase in resting metabolism measured by PET in this subregion. Aberrant white matter structures were evident in the second patient's DTI images but were not clinically correlated. We propose that axonal regrowth may underlie these findings and provide a biological mechanism for late recovery. Our results are discussed in the context of recent experimental studies that support this inference. [ABSTRACT FROM AUTHOR]

The mechanism of abdominal aortic aneurysm (AAA) formation remains incompletely described. AAA were created in the infrarenal aortas of 14 Yorkshire swine (25-35kg) using balloon dilation and luminal collagenase (8000u) and elastase (500u) perfusion. Positron emission tomography computed tomography (PET CT) was performed on post-operative days 1, 3, 7, 14, and 28 in 5 swine. Cellular uptake of 18-fluorodeoxyglucose (FDG) was quantified within AAA and sham segments of aorta using radioactive decay density within an ellipsoid volume of interest (VOI). Nine swine were euthanized at 1 (n=3), 3(n=l), 7(n=l), 14(n=l), 21(n=2) and 28(n=1) days for histological analysis (H&E, Masson's trichrome, and Verhoeff-van Giesen stain). AAA activity on day 7 (32.7%±22.3%) was significantly higher (p=0.01) than day one (-2.8±17.9%) and day 28 0.2±22.9%). Inflammatory response, smooth muscle cell regeneration, and the appearance of hyaline matrix deposition correlate to interval FDG activity of the AAA. Extensive elastin fiber disruption was evident at all time points. FDG uptake demonstrates increased local metabolic demand following mechanical and enzyme-induced AAA formation. Regression of relative FDG uptake at 28 days suggests that elastase induced injury may not be perpetual. PET CT may provide a useful method for longitudinal noninvasive measurements within a single animal for endovascular research. [ABSTRACT FROM AUTHOR]