Distribution of I-BZA (N-2-diethylaminoethyl-4-iodobenzamide) in grafted melanoma and normal skin: a study by secondary ion mass spectroscopy.

Iodobenzamides labelled with radioactive iodine are undergoing clinical evaluation as imaging and potential therapeutic agents in malignant melanomas. However, the uptake mechanism in melanic tissues remains controversial. Using secondary ion mass spectrometry (SIMS), we studied the microscopic distribution of N-(2 diethylaminoethyl)-4 iodobenzamide (I-BZA) in B16 murine melanoma inoculated to C57BL/6J1 Co mice as well as in normal pigmented skin. SIMS provides specific detection of iodine-127 atoms entering 127I-BZA composition. In B16 melanoma, 127I-BZA distribution was found to be heterogeneous, with focal areas of high concentration corresponding to cells rich in melanin pigments. In skin, SIMS analysis showed 127I-BZA distribution appearing as multiple small selective concentration areas within the epidermis. The number of these foci decreased from the stratum basale towards the stratum corneum. In both tissues, the intracellular location appeared specifically intracytoplasmic, with no apparent nuclear uptake. Distribution of this molecule mirrored that of melanin pigments. There was no enhancement of uptake at the membrane site. These results suggest that, in melanic tumors as well as in normal pigmented tissue, specific uptake of 127I-BZA occurs in pigment cells, with a possible link to melanin pigments.

Parathyroid imaging using simultaneous double-window recording of technetium-99m-sestamibi and iodine-123.

UNLABELLED: Technetium-99m-sestamibi represents an important advance in the scintigraphic location of parathyroid neoplasms. However, the optimal procedure for 99mTc-sestamibi parathyroid scanning has not been defined. The first objective of this work was to optimize the technical aspects of subtraction scanning, using simultaneous double-window recording of 99mTc-sestamibi and 1231 instead of successive image recording. The second objective was to compare two protocols for detecting abnormal parathyroid glands: subtraction scanning and single-tracer double-phase scanning. METHODS: Thirty patients referred for first surgery of primary hyperparathyroidism had both subtraction scanning and double-phase scanning in the same imaging session. Images of 99mTc-sestamibi and 123I were recorded simultaneously in nonoverlapping windows and then subtracted. For double-phase scanning, images of 99mTc-sestamibi, acquired 15 min and 120 min after tracer injection, were visually compared. Surgery disclosed a solitary adenoma in 27 patients, bilateral adenomata in 2 patients and 3 hyperplastic glands in the last patient. No patient had persistent hypercalcemia. RESULTS: Preoperative 99mTc-sestamibi/123I subtraction scanning located 25 of 27 solitary adenomas, the bilateral adenomata and 3 of 3 hyperplastic glands. The overall sensitivity for enlarged parathyroids was 94%, and the false-positive image rate was 3%. The 99mTc-sestamibi single-tracer technique located 22 of 27 solitary adenomas, the bilateral adenomata and 1 of 3 hyperplastic glands. Overall sensitivity was 79% and the false-positive image rate was 10%. The gamma camera imaging time was 30 min for the subtraction technique and 50 min for the single-tracer double-phase study. An ectopic adenoma in the sheath of the right carotid artery was detected by both techniques. CONCLUSION: These results, together with other data in the literature, indicate that 99mTc-sestamibi/123I subtraction imaging is accurate in locating enlarged parathyroids. Classical difficulties of this technique (motion artifacts and prolonged immobilization) were avoided by using simultaneous recording of the two isotopes. In this series subtraction imaging was more rapid and more sensitive (p < 0.04) than the single-tracer technique.

Cardiac axis change between prone and supine positioning may contribute to differences in 99Tc(m)-MIBI myocardial SPET imaging.

The aims of this study were to assess the effect of prone and supine positioning on 99Tc(m)-MIBI myocardial SPET images and the contribution of cardiac axis change. We compared 227 tomograms of patients imaged in the prone position with 227 tomograms of the same patients imaged in the supine position. For each tomographic session, the axis angle of the heart was recorded using an in-house program. The results showed a significant change in the cardiac axis angle of 9 degrees in the transaxial plane (P < 0.001). This change in the cardiac axis correlated with differences in cardiac wall activity (wall activity when the patient was imaged in the prone position minus wall activity when the patient was imaged in the supine position). Our results suggest that factors other than diaphragmatic movement and attenuation could account for the differences in wall activity observed when patients are imaged prone versus supine. Differences in the intensity of photon attenuation in the heart itself, depending on the cardiac axis, could be a contributing factor. Quantitation of the variation in wall activity leads us to suggest that 99Tc(m)-MIBI SPET should be performed in the prone position to allow better visualization of the inferior and the septal walls. The anterior and lateral walls are better studied in the supine position. Images acquired in both the prone and supine positions would allow the best assessment of all walls.

Subcellular distribution of a new fluorinated, biocompatible, non-ionic telomeric carrier: a study in cultured B16 melanoma and rat skin fibroblasts.

Tris-hydroxymethyl-amino-methane telomers bearing a fluorinated end have recently been proposed as potential drug carriers. Using ion microscopy, we have investigated the cell uptake and subcellular distribution of a perfluorinated telomere, called F-TAC, in two cell lines, malignant murine B16 melanoma and normal rat skin fibroblasts. Single layer cell cultures on gold plates were incubated with F-TAC at different concentrations. Ion microscopy using mass spectrometry enabled the detection of Fluorine 19 atoms entering into F-TAC constitution. This microanalytical study showed an elective cytoplasmic localization of the molecule, wherein the distribution is relatively homogeneous. Within same culture and incubation conditions, intercellular variations in F-TAC content were very low. In the malignant line, the intracellular concentration remains practically identical when increasing F-TAC concentration in the culture medium above 0.2 mg/ml, indicating that the uptake phenomenon is saturable. In conclusion, the F-TAC telomer easily crosses the plasma membrane, however, it has difficulties in crossing the nuclear membrane. It is likely that intracellular penetration is essentially due to rapid endocytosis of the telomer.

Localization of N-(2-diethylaminoethyl)4-iodobenzamide in the pigmented mouse eye: a microanalytical study.

The 123I-N-(2-diethylaminoethyl)4-iodobenzamide (123I-BZA) is a new radiopharmaceutical used for the scintigraphic imaging of malignant melanomas. The mechanism for BZA uptake in melanic tissues is still unknown. Two methods of microanalysis, secondary ion mass spectrometry and electron probe X-ray microanalysis, were used to determine tissue distribution and subcellular location of unlabelled BZA in the C57BL6/J1 co mouse eye. Microanalysis showed elective BZA uptake by the pigmented structures of the eye: choroidal melanocytes and retinal pigment cells, where it was specifically located within melanosomes. The tropism of BZA for melanic tumours, as well as for normal pigmented tissues, could be explained by a high affinity for the melanin pigment.