[Phase 2 clinical study of 123I-N-(2-diethylaminoethyl)-2-iodobenzamide in the diagnostic of primary and metastatic ocular melanoma]. / Etude clinique en phase 2 de la BZA2 (123IN-(2-diéthylaminoéthyl)-2-iodobenzamide) dans le diagnostic du mélanome malin oculaire et de ses métastases.

PURPOSE: Iodobenzamides are reported to possess an affinity for melanoma. A first selected compound, BZA, was studied in a phase 2 clinical trial on 159 patients as an imaging agent for the detection of primary melanoma and metastases with good results. We report the results of a second phase 2 clinical trial on 40 patients with a new radiopharmaceutical BZA2 (an orthoiodinated BZA analog), which was expected to provide quality images sooner after injection and with better imaging contrast. PATIENTS AND METHODS: Performance was evaluated in 40 patients classified with primary ocular lesions (12), suspicion of metastases of ocular or cutaneous origin (15), or with no known secondary lesion (13), and results were compared with conventional investigation techniques (ophthalmoscopy, ultrasonography, and angiography for ocular melanoma, whole-body CT scan and ultrasonography for metastases). RESULTS: No adverse events were recorded. The overall results on a per patient basis showed a sensitivity of 78% and a specificity of 95%. The four false negatives observed were ocular lesions (three with a thickness<3mm and one achromic), but all the proven secondary lesions were imaged. Moreover, negative BZA2 scintigraphy in cases of suspicious lesions led to the correction of two diagnoses: the prostatic origin of bone metastases and the endocrine tumor origin (APUD system) of an ocular lesion. DISCUSSION: BZA2 scintigraphy is an easy test with good tolerance. In the diagnosis of ocular primary melanoma, the sensitivity of the test is 64%, although limited by the thickness (3mm) and the pigmentation of the lesion. However, the BZA2 scintigraphy is a very useful test for the detection of melanoma metastases, with a sensitivity of 100% and a specificity of 95%. CONCLUSION: BZA2 scintigraphy showed good tolerance in patients and it appears promising for differential diagnosis, staging, and restaging of melanoma.

Joint scintigraphy in rabbits with 99mtc-N-[3-(triethylammonio)propyl]-15ane-N5, a new radiodiagnostic agent for articular cartilage imaging.

UNLABELLED: The aim of this study was to investigate joint scintigraphy in rabbits with 99mTc-N-[3-(triethylammonio)propyl]-15ane-N5 (NTP 15-5), a new radiopharmaceutical that specifically localizes in cartilaginous tissues. METHODS: Scans obtained after intravenous injection of the 99mTc-labeled compound in normal and arthropathy-induced rabbits were compared with those of the bone-imaging agent 99mTc-methylene diphosphonate (99mTc-MDP). RESULTS: The radioactive uptake of 99mTc-NTP 15-5 was detected in cartilaginous tissues 5 min after injection and was stable for 2 h. The uptake intensity was related to age and joint disease severity, and cartilage alterations not revealed by radiography induced a significant decrease of radiotracer uptake. On the other hand, imaging performed with 99mTc-MDP did not reveal the early changes in arthrosis but was more specific for bone remodeling in advanced stages of diseases or in inflammatory processes. CONCLUSION: Our results indicate that 99mTc-NTP 15-5 could be a good tracer for human arthrosic and arthritic cartilage detection, especially for the early diagnosis of joint diseases.

Study of implanted biomaterial functionality by diphosphonate molecules labeled with radioactive 99mTc.

An implanted biomaterial can be transformed into young bone after some months, but it has not necessary reached full biofunctionality. Mineral concentration kinetics and crystal-structure studies, still being carried out in our group, are completed here by biofunctionality determinations. A natural coral is implanted in vivo at the cortical level of the femoral diaphyoff++ in rabbits. Diphosphonates molecules labeled with radioactive 99mTc are then injected in rabbits and the fixation of the radioactivity is analyzed in several sites for 8 mo after the implantation. Nuclear instruments and methods are used for the measurements. Four successive cycles of osseous remodeling are determined before reaching a biofunctional phase.

Clinical study of [123I] N-(2-diethylaminoethyl)-4-iodobenzamide in the diagnosis of primary and metastatic ocular melanoma.

PURPOSE: To assess the value of scintigraphy with [123I]N-(2-diethylaminoethyl)-4-iodobenzamide (BZA), a phase II clinical trial was performed on 48 patients with a suspicion of ocular melanoma. METHODS: 56 examinations were performed to image lesions with a clinical diagnosis of primary ocular melanoma before and/or after treatment, to observe the results in simulating lesions or to image metastases. RESULTS: Ocular BZA-scintigraphy demonstrated a sensitivity of 86%, and a specificity of 83%. Whole-body scintigraphy was used in the follow-up of treated patients and could be repeated. We imaged orbital recurrence, known and occult metastases, specially in the liver. After 9 conservative treatments ocular BZA-scintigraphy was negative in 9 eyes. CONCLUSION: The BZA-scintigraphy in combination with other diagnostic procedures appeared to be a suitable method in the diagnosis of ocular melanoma and a potentially useful imaging modality to screen for ocular malignant melanoma metastases.

Application of textural features to the detection of ocular melanomas in scintigraphy.

A method for automated detection of ocular melanoma in scintigraphic images is described. The algorithm first performs an automatic segmentation of the eyes on specific reference images. The images of the eyes are then analyzed using textural parameters computed in several directions and averaged to damp directional information. Assuming that only one eye per patient will be pathological, the ratio of the textural parameters of the two eyes is computed. A statistical analysis is performed over these ratios to select the most highly discriminating textural parameters and detect the pathological patients. The method has been tested successfully on a population of 23 individuals and we found significant differences between pathological and normal patients.

A radiolabelled iodobenzamide for malignant melanoma staging.

123I-N-(di-ethylamino-2-ethyl) 4 iodobenzamide (I-BZA) has been put forward by the Clermont-Ferrand INSERM U71 group (France) as a tracer for malignant melanoma. We report on the clinical results obtained in 56 studies performed on 48 patients. Whole body scans along with spot views were obtained after injection of 185 MBq of I-BZA. The scans were read by three independent observers and correlated to the clinical findings and the other imaging modalities available, taking into account all lesions larger than 1 cm. Patients were classified into two groups on the basis of a post-treatment survey of patients: group I, in complete remission (24 scans); group II: documented metastases (32 scans). In group 1, 21 studies were truly negative. However, three studies showed positive results. Only one turned out to be a false positive (specificity 95%), the other two revealed unknown lesions and modified the patients' management. In group II, 73% of the known metastases were detected with higher sensitivities (> 80%) for eye and orbit, lung and abdomen. One false positive was reported and four new lesions were detected. I-BZA scintigraphy has the same sensitivity as immunoscintigraphy with higher specificity and without the risk of xenoimmunization. It is a useful tool for staging malignant melanoma which can improve patient management.

Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide).

Preclinical studies established [125I]-N-(2-diethylaminoethyl) 4-iodobenzamide (BZA) as a potential radiopharmaceutical in the management of patients with malignant melanoma. External detection of both murine and human melanotic melanomas was possible after intravenous injection of 125I-BZA in tumor-bearing mice. This article reports a Phase II clinical trial evaluating 123I-BZA as an imaging agent of primary melanomas and metastases. A total of 110 patients with a history of melanoma were investigated in two nuclear medicine departments. Subjects were imaged from 20 to 24 hr after the intravenous injection of 3.5 mCi (130 MBq) of 123I-BZA. After injection, no short-term or long-term side effects were noted. Calculated on a lesion-site basis, diagnostic sensitivity was 81%, accuracy was 87% and specificity was 100%. The melanoma nature of previously occult lesions was confirmed by clinical criteria and/or additional investigations in follow-up studies. The scintigraphies were normal in 44 patients in clinical remission after treatment of malignant melanoma and in seven patients with nonmelanoma disease. No false positive results were observed. Iodine-123-BZA scintigraphy appears to be a safe and useful agent for the detection and follow-up of patients with malignant melanoma. BZA also allowed the detection of unsuspected lesions and the evaluation of the results of various therapeutic procedures such as surgery, chemotherapy, immunobiology, biological therapy or radiotherapy.

Synthesis and evaluation of new iodine-125 radiopharmaceuticals as potential tracers for malignant melanoma.

The synthesis, labeling, and biodistribution of four 125I radiopharmaceuticals designed to localize in melanoma were tested. Uptake in tumors was demonstrated by autoradiography of whole-body sections and quantitated by measurement of radioactivity of selected tissues and tumors using melanoma-bearing mice. N-(2-diethylaminoethyl)-4-iodobenzamide was selected for its highest melanoma uptake: 60 min after IV injection of 6.5% and 4% ID/g, respectively for murine B16 and human melanotic melanoma. Tumor uptake showed the highest values of all analyzed tissues from 6 to 24 hr after injection. High uptake in melanotic tumor tissue with relatively low uptake in blood, muscle, brain, lung, and liver tissue resulted in high tumor/nontumor ratios (at 24 hr for B16, tumor/blood = 37, tumor/brain = 147, tumor/muscle = 95). This agent was compared with iodoamphetamine. Scintigraphic images of the tumor confirmed that external detection of melanoma is possible with this new radiopharmaceutical.

[Simultaneous study of the placental, myometrial and cervical circulations (indium 113 and anemometric thermometry). 3). Double blind study of the action of intravenous ritodrine during normal pregnancy]. / Etude simultanée des circulations placentaire, myométriale et cervicale. (indium 113 et thermométrie anémométrique) 3) Etude en double aveugle de l'action de la ritodrine intra-veineuse au cours de la grossesse normale

The authors measure the changes in placental and myometrial blood flow using an isotope technique with Indium 113. They calculate an index of the variation in placental blood flow (I.V. D.P.) and an index of variation of myomoetfrial blood flow (I.V.D.M.) after injecting Ritodrine or a placebo between the 28th and the 36th week of pregnancy. This study was carried out in 26 normal women. At the same time using Brotanek's technique changes in the cervical blood flow were registered. No change in the placental, myometrial or cervical blood flows were noted while Ritodrine was being transfused intravenously.

[Incidence of deep venous thromboses in traumatology and methods of early detection]. / Fréquence des thromboses veineuses profondes en traumatologie et méthodes de dépistage précoce

In this work carried out at the Traumatology Centre in Strasbourg, out of 227 patients operated for a fracture situated between the pelvis and the tibial plateau, the authors endeavoured to show a thrombosis of the lower limbs. The means of exploration included in addition to the clinical and biological blood tests an isotopic, rheographic and phlebographic surveillance. The latter three ways of exploration are particularly viewed in this study, during which it was possible to demonstrate 44 p. 100 thrombo-embolic manifestations of which 38 p. 100 were detected only by the isotopic method, the phlebographic check for its part confirming 80 p. 100 of the clinically undeclared cases of thrombosis.