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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Synthesis and evaluation of new iodine-125 radiopharmaceuticals as potential tracers for malignant melanoma. 186 82

In the sequence of our studies on radiopharmaceuticals for malignant melanoma detection the results were most promising for the possible use of 125I or 123I-N-(2-diethyl amino ethyl)4-iodobenzamide. The biodistribution in mice bearing melanoma either human or animal from 4 to 24 hrs. post i.v. injection showed high uptake in tumor tissue together with relatively low uptake in muscle, brain, lung and liver. Scintigraphic images of the tumor obtained at the same times confirmed that melanoma detection was very promising.
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PMID:[Perspectives of scintigraphic diagnosis of malignant lymphoma using a new radiopharmaceutical]. 212 23

In order to develop improved radiopharmaceuticals for imaging malignant melanoma, we have synthesized and characterized 125I-and 131I-labeled (2-piperidinylaminoethyl)4-iodobenzamide (PAB). In vitro binding profiles of IPAB and N-(2-diethylaminoethyl)4-iodobenzamide (IDAB, a structurally related analog of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and IDAB possessed a high sigma-1 affinity and a low affinity for sigma-2 sites. In vitro homologous competition binding studies of [125I]PAB with human malignant melanoma cell A2058 showed that the tracer was bound to the cells with a high affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution studies in nude mice implanted with human malignant melanoma xenografts showed good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24 hr) of [125I]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01, respectively. Tumor imaging with [131I]PAB in a nude mice model xenografted with human malignant melanoma at 24 hr clearly delineated the tumor with very little activity in any other organ. These results demonstrate that sigma-1 receptors could be used as external markers for malignant melanoma.
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PMID:A malignant melanoma imaging agent: synthesis, characterization, in vitro binding and biodistribution of iodine-125-(2-piperidinylaminoethyl)4-iodobenzamide. 825 5

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.
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PMID:Phase II scintigraphic clinical trial of malignant melanoma and metastases with iodine-123-N-(2-diethylaminoethyl 4-iodobenzamide). 832 82

To improve the radiolabeling yield and the specific activity of [125I]N-(2-diethylaminoethyl)-4-iodobenzamide (DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [125I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [125I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung, was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma.
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PMID:An improved synthesis of [125I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma. 846 82

N-(2-Diethylaminoethyl)-4-iodobenzamide (BZA) is a radiopharmaceutical recently developed in our laboratory for the scintigraphic detection of melanoma and metastases. Optimal time for imaging was between 18-24 h p.i. of [123I] BZA. With a view to selecting compounds able to provide quality images shortly after the injection, synthesis of an initial series of BZA derivatives and their evaluation in B16 melanoma bearing mice have been carried out. The [125I] radiolabeled products were obtained by a simple isotopic exchange procedure with high radiochemical yields (85-95%). After i.v. administration of the compounds we observed a good tumoral targeting ability. Tumoral activity peaked at 2.6 to 7.70% injected dose per g within 1 h post-injection. One of the benzamides with a blood clearance faster than that of BZA--0.06 vs. 0.2% I D/g--6 h p.i. gave the same tumor to blood and to organ ratios as BZA at 12-18 h p.i. Based on these preclinical data we hope to obtain good tumoral images 6 h p.i. in scintigraphic studies in man.
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PMID:Synthesis, radiolabeling, and preliminary evaluation in mice of some (N-diethylaminoethyl)-4-iodobenzamide derivatives as melanoma imaging agents. 853 34

AMBIS 4000, a multi-wire proportional counter, was calibrated for iodine-125 measurements. The detector displayed a linear response over a wide dynamic range. Using whole-body mice cryosections, a linear relationship could be established between count rate per area (cpm/mm2) measured with the AMBIS 4000 detector and the count rate per gram (dpm/g) determined with an NaI(Tl) scintillation detector. A calibration curve could, thus be constructed. This new method allowed direct visual and quantitative evaluation of the biodistribution of a short series of 125I-labelled benzamides in melanoma-bearing mice. All the compounds studied showed good tumoral targeting ability. For one of them, ortho-N-(2-diethylaminoethyl)-4-iodobenzamide, liver and lung uptake decreased rapidly after dosing, making it a suitable tracer for scintigraphic detection of malignant melanoma.
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PMID:Evaluation in mice of some iodinated melanoma imaging agents using cryosectioning and multi-wire proportional counting. 1038 93

[123I]-N-(2-Diethylaminoethyl)-4-iodobenzamide (123I-BZA) has been the best scintigraphic agent described so far for malignant melanoma and ocular melanoma diagnosis. We replaced 123I by the more convenient radioisotope 99mTc and synthesized four bis(aminoethanethiol) derivatives. We describe the synthesis of a new oxo-technetium complex (TcO-Cf), prepared in very high yield (radiochemical yield > 95%), that exhibits an affinity for the pigmented tumor cells. This complex was evaluated in vivo in mice bearing C57Bl6 murine melanoma. After injection, a rapid decrease in the radioactivity levels was noted for all tissues and organs except for eyes (1.26 %ID/g at 1 h and 2.69 %ID/g at 24 h postinjection) and the tumor (1.19 %ID/g at 1 h and 0.80 %ID/g at 24 h postinjection), suggesting a specific in vivo binding of this complex to the pigmented cells. These results were compared with those already published for three other technetium-99m bis(aminothiol) complexes with benzamide derivatives.
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PMID:Synthesis and biodistribution of a new oxo-technetium-99m bis(aminothiol) complex as a potential melanoma tracer. 1129 57

Iodobenzamides are reported to possess some affinity for melanoma. In order to identify the compound having the most appropriate pharmacokinetic properties as a potential melanoma imaging agent, thirteen new [125I]radioiodobenzamides with a butylene amide-amine spacer and various substituents on the terminal amino group were investigated. Their synthesis, radioiodination and biodistribution in B16 melanoma bearing C57BL6 mice are described and compared to [125I] labeled N-(2-diethylaminoethyl)-4-iodobenzamide ([125I]BZA), our reference compound. Changes in the terminal amino constituents induced modifications of lipophilicity, tumor uptake and organ distribution. The dimethylaminobutyl iodobenzamide appeared to be the most promising radiopharmaceutical imaging agent for the detection of melanoma and its metastases.
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PMID:Synthesis, characterization and comparative biodistribution study of a new series of p-iodine-125 benzamides as potential melanoma imaging agents. 1157 1

The cellular uptake and incorporation in macromolecules of iodine-125 labelled N-(2-diethylaminoethyl)-4-iodobenzamide ([125I]BZA), a melanoma imaging agent, was studied using human melanoma cells M3Dau (amelanotic) and M4Beu (melanotic). The interaction between [125I]BZA and synthetic melanin was examined in various conditions of incubation. The results showed that uptake was high only for M4Beu, whereas the incorporation in trichloroacetic acid-precipitable proteins was very low for both model cell lines, with no correlation with melanin content. Experiments with synthetic melanin showed that BZA binding to melanin was saturable and reversible, and involved several types of interaction. The influence of the ionic environment indicated that electrostatic forces play a role in the affinity, and the decrease in binding produced by the presence of an alcohol in the medium suggested that hydrophobic interactions may be involved in the binding mechanism. This was supported by the Scatchard analysis, which revealed two classes of binding sites, and the determination of two association constants (K1 = 3.9 +/- 1.9 x 106/M and K2 = 2.9 +/- 0.9 x 104/M). The affinity of BZA for melanin might explain the good results obtained in a phase II clinical trial for the diagnosis of malignant melanoma metastases, in which the specificity was 100%.
Melanoma Res 2002 Apr
PMID:Melanin affinity of N-(2-diethylaminoethyl)-4-iodobenzamide, an effective melanoma imaging agent. 1193 Jan 7


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