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Purpose: Here, we report a new and rapid radiosynthesis of F- N-[2-(diethylamino)ethyl]-6-fluoro-pyridine-3-carboxamide ([F]ICF01006), a molecule with a high specificity for melanotic tissue, and its evaluation in a murine model for early specific detection of pigmented primary and disseminated melanoma. Methods: [F]ICF01006 was synthesized using a new one-step bromine-for-fluorine nucleophilic heteroaromatic substitution. Melanoma models were induced by subcutaneous (primary tumour) or intravenous ( lung colonies) injection of B16BL6 melanoma cells in C57BL/6J mice. The relevance and sensitivity of positron emission tomography (PET) imaging using [F]ICF01006 were evaluated at different stages of tumoural growth and compared to F-fluorodeoxyglucose ([F]FDG). Results: The fully automated radiosynthesis of [F]ICF01006 led to a radiochemical yield of 61 % and a radiochemical purity >99 % (specific activity 70-80 GBq/μmol; total synthesis time 42 min). Tumours were visualized before they were palpable as early as 1 h post-injection with [F]ICF01006 tumoural uptake of 1.64 ± 0.57, 3.40 ± 1.47 and 11.44 ± 2.67 percentage of injected dose per gram of tissue (%ID/g) at days 3, 5 and 14, respectively. [F]ICF01006 PET imaging also allowed detection of melanoma pulmonary colonies from day 9 after tumour cell inoculation, with a lung radiotracer accumulation correlated with melanoma invasion. At day 21, radioactivity uptake in lungs reached a value of 5.23 ± 2.08 %ID/g (versus 0.41 ± 0.90 %ID/g in control mice). In the two models, comparison with [F]FDG showed that both radiotracers were able to detect melanoma lesions, but [F]ICF01006 was superior in terms of contrast and specificity. Conclusion: Our promising results provide further preclinical data, reinforcing the excellent potential of [F]ICF01006 PET imaging for early specific diagnosis and follow-up of melanin-positive disseminated melanoma. [ABSTRACT FROM AUTHOR]

Purpose: Preclinical data pointed to Tc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify Tc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone Tc-hydroxymethylene diphosphonate (HMDP) radiotracer. Methods: Three osteoarthritic human tibial plateaux and four tibiofemoral joints were incubated with Tc-NTP 15-5 and Tc-HMDP for 2 h. Affinity of tracers for cartilage was determined by visual analysis of SPECT/CT acquisitions and measurement of cartilage to cortical bone uptake ratios. Results: Cartilage to cortical bone uptake ratios were 3.90 ± 2.35 and 0.76 ± 0.24, respectively, for Tc-NTP 15-5 and Tc-HMDP radiotracers. Visual analysis of fused SPECT/CT slices showed selective, intense Tc-NTP 15-5 accumulation in articular cartilage, whereas Tc-HMDP binding was low. Interestingly, a cartilage defect visualized on CT was clearly associated with focal decreased uptake of Tc-NTP 15-5. Conclusion: The tracer Tc-NTP 15-5 is of major interest for human cartilage molecular imaging and could find clinical applications in osteoarthritis staging and monitoring. [ABSTRACT FROM AUTHOR]

The usefulness of preoperative radionuclide scanning of the parathyroid glands in patients with primary or secondary hyperparathyroidism was long controversial because available techniques were of limited diagnostic efficacy. Technetium-99m-labeled sestamibi (99Tc-sestamibi) is a new radiopharmaceutical agent easily detected by gamma cameras. The first parathyroid imaging studies done with 99Tc-sestamibi about 10 years ago used a double-phase technique to separate thyroid and parathyroid tissue. Although promising, this method was less than ideal, particularly in multiple gland primary hyperparathyroidism and in secondary hyperparathyroidism. For several years, we have been using subtraction between two images acquired simultaneously, one with 99Tc-sestamibi, which binds to thyroid and parathyroid tissue, and the other with 123-iodine, which binds only to thyroid tissue. The remarkable efficacy of this technique in both primary and secondary hyperparathyroidism invites a reappraisal of the place of radionuclide imaging as a preoperative localization procedure done to reduce the need for repeat surgery. The usefulness of this technique in selecting candidates for unilateral surgery among patients with primary hyperparathyroidism is discussed. [Copyright &y& Elsevier]

Our lab developed (99m)Tc-NTP 15-5 radiotracer as targeting proteoglycans (PGs) for the scintigraphic imaging of joint. This paper reports preclinical results of (99m)Tc-NTP 15-5 imaging of an orthotopic model of Swarm rat chondrosarcoma (SRC). (99m)Tc-NTP 15-5 imaging of SRC-bearing and sham-operated animals was performed and quantified at regular intervals after surgery and compared to bone scintigraphy and tumoural volume. Tumours were characterized by histology and PG assay. SRC exhibited a significant (99m)Tc-NTP 15-5 uptake at very early stage after implant (with tumour/muscle ratio of 1.61 ± 0.14), whereas no measurable tumour was evidenced. As tumour grew, mean tumour/muscle ratio was increased by 2.4, between the early and late stage of pathology. Bone scintigraphy failed to image chondrosarcoma, even at the later stage of study. (99m)Tc-NTP 15-5 imaging provided a suitable set of quantitative criteria for the in vivo characterization of chondrosarcoma behaviour in bone environment, useful for achieving a greater understanding of the pathology.

The first study evaluating directly by the referring physician the clinical impact of [18F]-FDG-PET on modification of patient's management was performed only recently in California by means of a questionnaire. We have used the same methodology to evaluate this clinical impact during the opening year of our PET centre in France. A questionnaire was sent to the referring physician of each of the 476 patients who had at least one routine FDG-PET examination during the year 2000. Of 348 responses (response rate = 73%), the disease was upstaged in 26% of the cases and down-staged in 9%. Intermodality management changes (change from a scheduled therapeutic modality for a different one) were reported in 37% of the cases and intramodality changes in 9%. Those modification rates were respectively 38% and 7% in recurrence of colorectal cancer (153 patients), 47% and 7% in lung cancer (118 patients), 16% and 23% in lymphoma (43 patients), 25% and 6% in the staging of head and neck cancers (32 patients). When comparing with the corresponding studies performed in California, there were no significant differences between the rates of intermodality management changes. In contrast, intramodality management changes were less frequent in our survey, except for lymphoma. Globally, the clinical impact of FDG PET was similar with a higher response rate in our study (73% versus 35%); it was above the mean rate derived from a recent meta-analysis in more than 5,000 patients.