Studies on the binding of chlorpromazine and chloroquine to melanin in vivo

Tjälve, Hans; Nilsson, M.; Larsson, Bengt

doi:10.1016/0006-2952(81)90021-6

Cited by 48 publications

(31 citation statements)

References 6 publications

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“…In contrast, the s-receptor ligand DTG did not inhibit B16 cell growth (33). Moreover, chloroquine (34) and phenothiazine derivatives have been reported to have a high affinity for melanin and to accumulate in pigmented cells of eyes (35,36). Some in vitro studies were not conclusive in their ability to show the haloperidol inhibition of 125 I-BZA binding to B16 pigmented cells (26).…”

Section: Discussionmentioning

confidence: 91%

Preparation and Biologic Evaluation of a Novel Radioiodinated Benzylpiperazine, 123I-MEL037, for Malignant Melanoma

Pham¹,

Berghofer²,

Liu³

et al. 2007

Journal of Nuclear Medicine

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Radiopharmaceuticals that can target the random metastatic dissemination of melanoma tumors may present opportunities for imaging and staging the disease as well as potential radiotherapeutic applications. A novel molecule, 2-(2-(4-(4-123 Iiodobenzyl)piperazin-1-yl)-2-oxoethyl)isoindoline-1,3-dione (MEL037), was synthesized, labeled with 123 I, and evaluated for application in melanoma tumor scintigraphy and radiotherapy. Methods: The tumor imaging potential of 123 I-MEL037 was studied in vivo in C57BL/6J female mice bearing the B16F0 murine melanoma tumor and in BALB/c nude mice bearing the A375 human amelanotic melanoma tumor by biodistribution, competition studies, and SPECT. Results: 123 I-MEL037 exhibited high and rapid uptake in the B16F0 melanoma tumor at 1 h (13 %ID/g [percentage injected dose per gram]), increasing with time to reach 25 %ID/g at 6 h. A significant uptake was also observed in the eyes (2 %ID, at 3-6 h after injection) of black mice. No uptake was observed in the tumor or in the eyes of nude mice bearing the A375 tumor. Because of high uptake and long retention in the tumor and rapid body clearance, the mean contrast ratios (MCR) of 123 I-MEL037 were 30 and 60, at 24 and 48 h after injection, respectively. At 24 h after injection of mice bearing the B16 melanoma, SPECT indicated that the radioactivity was located predominately in the tumor followed by the eyes, whereas no specific localization of the radioactivity was noted in mice bearing the A375 human amelanotic tumor. In competition experiments, uptake of 123 I-MEL037 in brain, lung, heart, and kidney-organs known to contain s-receptors-was not significantly different in haloperidol-treated animals compared with control animals. Therefore, reduction of uptake in tumor and eyes of the pigmented mice bearing the B16F0 tumor suggested that the mechanism of tumor uptake was likely due to an interaction with melanin. Conclusion: These findings suggested that 123 I-MEL037, which displays a rapid and very high tumor uptake, appeared to be a promising imaging agent for detection of most melanoma tumors with the potential for development as a therapeutic agent in melanoma tumor proliferation.

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Section: Discussionmentioning

confidence: 91%

Preparation and Biologic Evaluation of a Novel Radioiodinated Benzylpiperazine, 123I-MEL037, for Malignant Melanoma

Pham¹,

Berghofer²,

Liu³

et al. 2007

Journal of Nuclear Medicine

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show abstract

“…These interactions are complex and depend on diverse factors, such as cysteine content, pH, and ionic interactions (79). As described above for synthetic DOPA melanin, Scatchard plot analysis has revealed the heterogeneity of binding sites on melanin for single compounds (69,102,122,123). The conformation of the compounds may also influence these interactions.…”

Section: Binding Of Compounds By Melanin In Humans In Vivomentioning

confidence: 87%

Impact of Melanin on Microbial Virulence and Clinical Resistance to Antimicrobial Compounds

Nosanchuk

Casadevall

2006

Antimicrob Agents Chemother

360

284

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“…That is, in acute toxicity experiments in animal models, the dose at which 50 % die (LD 50 ) is approximately twice as high with hydroxychloroquine as with chloroquine (see Chap. 3 ) [ 11 ].…”

Section: Clinical Uses and Dosingmentioning

confidence: 99%