Synthesis and preclinical evaluation of BOLD-100 radiolabeled with ruthenium-97 and ruthenium-103.

BOLD-100 (formerly IT-139, KP1339), a well-established chemotherapeutic agent, is currently being investigated in clinical trials for the treatment of gastric, pancreatic, colorectal, and bile duct cancer. Despite numerous studies, the exact mode of action is still the subject of discussions. Radiolabeled BOLD-100 could be a powerful tool to clarify pharmacokinetic pathways of the compound and to predict therapy responses in patients using nuclear molecular imaging prior to the therapy. In this study, the radiosyntheses of carrier-added (c.a.) [97/103Ru]BOLD-100 were performed with the two ruthenium isotopes ruthenium-103 (103Ru; ß-, γ) and ruthenium-97 (97Ru; EC, γ), of which in particular the latter isotope is suitable for imaging by single-photon emission computed tomography (SPECT). To identify the best tumor-to-background ratio for diagnostic imaging, biodistribution studies were performed with two different injected doses of c.a. [103Ru]BOLD-100 (3 and 30 mg kg-1) in Balb/c mice bearing CT26 allografts over a time period of 72 h. Additionally, ex vivo autoradiography of the tumors (24 h p.i.) was conducted. Our results indicate that the higher injected dose (30 mg kg-1) leads to more unspecific accumulation of the compound in non-targeted tissue, which is likely due to an overload of the albumin transport system. It was also shown that lower amounts of injected c.a. [103Ru]BOLD-100 resulted in a relatively higher tumor uptake and, therefore, a better tumor-to-background ratio, which are encouraging results for future imaging studies using c.a. [97Ru]BOLD-100.

Multisystem sarcoidosis and carcinoma of the uterine cervix: an unusual association.

Sarcoidosis malignancy syndrome is a rare phenomenon which remains controversial. We report here the case of a 46-year-old woman presenting with multisystem sarcoidosis 12 months after the completion of combined treatment for stage III squamous cell carcinoma of the uterine cervix; at the time she was still in complete remission of the tumor. The outcome was rapidly favorable under oral corticosteroid therapy. The time interval between the two illnesses as well as patient's age strongly suggest a relationship. Possible pathophysiologic mechanisms and the literature regarding uterine tumors are briefly reviewed.

Angiosarcoma variant of Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome is characterized by the occurrence of disseminated intravascular coagulation (DIC) usually caused by benign angiomatous tumours. Here we report the case of a 70-year-old man in whom DIC revealed a locally advanced hepatic tumour. Although DIC resolved with heparin, antithrombin III, fresh frozen plasma and corticosteroids, the patient died from haemoperitoneum following a fall, 3 months after the initial observation. Histopathological examination by autopsy allowed the diagnosis of hepatic angiosarcoma. The physiopathogenic mechanisms and treatment options are discussed.

Hemophagocytic Syndrome Induced by HIV.

Hemophagocytic syndrome is an unusual illness due to the proliferation of activated macrophages phagocyting the hematopoietic cells. This syndrome has been reported in association with infectious agents, lymphoproliferative diseases, immunosuppressive conditions or auto-immune illnesses. Cytokines secreted by activated or neoplastic lympho-cytes activate the macrophages. Autocrine and paracrine mechanisms take over and could explain resistance to therapy. Some viruses, including EBV, could upregulate cytokine genes. This report describes an adult with HIV-infection presenting with severe hemophagocytic syndrome in whom an extensive evaluation did not reveal opportunistic disease and suggests that the cause was the HIV. The outcome was fatal and highlights the poor prognosis of hemophagocytic syndrome in this context.

Primary Hyperparathyroidism and Lymphoproliferative Diseases: Three Case Reports.

Pathophysiologic mechanisms of malignancy-associated hypercalcemia are varied. The association of neoplasia and primary hyperparathyroidism (PHP) has been illustrated by clinical cases and by epidemiologic studies which have pointed to an increased risk of different malignancies during PHP. The authors report two cases of monoclonal gammapathy and one case of chronic lymphocytic leukemia (CLL) associated with PHP. A 58-year-old man presented with hypercalcemia due to PHP after remission for multiple plasmacytoma was obtained. A 70-year-old man was hospitalized for malaise, studies showed major hypercalcemia and benign monoclonal gammapathy. In the two cases, resolution of hypercalcemia was obtained by parathyroidectomy. The third patient was a 84-year-old woman with CLL who continued to deteriorate despite response to therapy, further studies confirmed hyperparathyroidism Physiopathogenic mechanisms of this association are discussed. The PHP-malignancy association should be considered ifthe symptoms or outcome of anyone of the two diseases are atypic.

Autoimmune cytopenias associated with malignancies and successfully treated with intravenous immune globulins: about two cases.

The authors report on the cases of two adult male patients presenting with autoimmune cytopenias associated with malignancies: a case of autoimmune haemolytic anemia occurring after remission of Hodgkin's disease and a case of autoimmune neutropenia in the setting of renal carcinoma. High-dose intravenous immune globulins (IIG) administered after failure of corticosteroid therapy produced a rapid and long-lasting response. These cases illustrate that intravenous immunoglobulins may be helpful in refractory cases of autoimmune cytopenias. The association of IIG and corticosteroid could be synergistic and effective independently of the outcome of the underlying disease. The pathophysiogenic mechanisms and literature are discussed briefly.

Opportunistic infection with Rhodotorula in cancer patients treated by chemotherapy: two case reports.

Rhodotorula species are commensal yeasts of variable pathogenicity. The authors report the case histories of two patients presenting with febrile neutropenia. The first was a 3-year-old girl who had been treated with combination chemotherapy for a tumour of the posterior fossa. The second was a 46-year-old man who had received chemotherapy for lymphoplasmocytic lymphoma, followed by consolidation treatment with autologous bone marrow transplantation. Investigation revealed infection caused by Rhodotorula. The outcome was favourable after removal of the catheter in both patients. Rhodotorula species have been isolated during a variety of infectious complications. Almost all published cases of fungaemia concern patients with central venous catheters that have been in place over long periods, who have also been treated with broad spectrum antibiotics. Neoplasia represents the most frequent underlying disease. The pathogenicity of Rhodotorula species appears to be moderate in most cases; fungal therapy or the removal of infected catheters is generally effective. Nevertheless, Rhodotorula has been reported to provoke fatal endocarditis or meningitis and can probably cause septic shock.