123 I- N -(2-diethylaminoethyl)-2-iodobenzamide: a potential imaging agent for cutaneous melanoma staging

Abstract

Melanoma is a neoplasia of dramatically increasing incidence that has a propensity to spread rapidly. Early detection is fundamental and patient management requires reliable, sensitive and reproducible staging methods, such as a single examination by planar scintigraphy or single-photon emission tomography (SPET) using a radiopharmaceutical with selectivity for melanoma tissue. Among iodobenzamides reported to possess an affinity for melanoma, a new compound, N-(2-diethylaminoethyl)-2-iodobenzamide (BZA(2)), was selected for a clinical trial in view of its pharmacokinetic experimental profile in melanoma-bearing mice. Planar whole-body scintigraphy using (123)I-BZA(2) was performed in 25 patients with histologically proven cutaneous melanoma. Performance was evaluated in two groups of patients with one or more documented secondary lesions ( n=13) or with no known secondary lesions ( n=12), and results were compared with those of conventional investigation techniques. No adverse clinical or biological events were recorded. Lesions were imaged by increased tracer uptake, and good quality images were obtained 4 h after administration. After a follow-up of more than 1 year, the overall results of (123)I-BZA(2) scintigraphy on a per patient basis showed a sensitivity of 100%, a specificity of 95%, a positive predictive value of 86% and a negative predictive value of 100%. The proven secondary lesions were imaged with a sensitivity of 100% and a specificity of 91%. In seven patients with suspected metastases, the absence of (123)I-BZA(2) uptake was confirmed as true negative, and in one patient without suspected metastases, (123)I-BZA(2) scintigraphy revealed a gastric lesion. Hence eight diagnoses would have been modified by (123)I-BZA(2) scintigraphy data. (123)I-BZA(2) allowed discrimination between benign and malignant lesions and, in the case of malignancies, between those of melanomatous origin and others. This compound, which is selective for melanoma tissue, appears promising for the staging and restaging of melanoma.

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

“…Moreover, the iodobenzamides 123 I-N-(2-diethylaminoethyl) 4-iodobenzamide ( 123 I-BZA) (7), 123 I-N-(2-diethylaminoethyl)-2-iodobenzamide ( 123 I-BZA2) (11,12), and 123 I-iodobenzamide ( 123 I-IBZM) (13) and the iodobenzylamine N-[3-(4-morpholino)propyl]-N-methyl-2-hydroxy-5-iodo-3-methylbenzylamine (ERC9 (14) have been evaluated in melanoma patients, resulting in excellent detection of melanoma and its metastases with high sensitivity and selectivity. These studies confirmed the efficacy of these iodinated radiopharmaceuticals as useful imaging agents in patients with cutaneous and ocular melanoma on the basis of the selective high affinity binding to melanin-containing melanocytes.…”

[99mTcOAADT]-(CH2)2-NEt2: A Potential Small-Molecule Single-Photon Emission Computed Tomography Probe for Imaging Metastatic Melanoma

“…Small technetium-labeled molecules based on the structural elements of the iodobenzamides currently in clinical trials for melanoma detection (11,12,14) have also been identified as possessing high in vivo melanoma accumulation. [ 99m Tc]oxotechnetium(V) complexes of tetradentate N 2 S 2 (AADT) chelates containing only tertiary amine substituents have considerable melanoma affinity (18,(20)(21)(22), with 99m Tc-1 displaying an in vivo melanoma uptake of 7.6% ID/g (melanoma/ nontarget tissue = 9.5) at 1 hour postinjection in the s.c. C57BL6/B16F0 mouse model (20).…”

“…Among these SPECT agents, the most promising are the radioiodinated benzamides (10)(11)(12)(13)(14). Although the nature of the affinity of iodobenzamides for melanoma is not clearly understood, it has been shown that radiolabeled iodobenzamides possess a considerable in vivo affinity for melanotic melanoma lesions compared with amelanotic lesions (10) 123 I]BZA at 1 hour postinjection and a 4-fold higher ratio at 4 hours in the C57BL6 mouse model (12,13).…”

“…More recently, a single-center clinical trial in 25 patients using another radioiodinated iodobenzamide derivative, N-(2-diethylaminoethyl)-2- Fig. 1), showed 100% sensitivity, 95% specificity, a positive predictive value of 86%, and a negative predictive value of 100% on a per patient basis (14).…”

Resin-supported arylstannanes as precursors for radiolabeling with iodine: benzaldehydes, benzoic acids, benzamides, and NHS esters

“…[32][33] In particular, structural analogues of N,N-dialkylamino-alkyl iodobenzamides with positional isomers of the halide, with different mono-and di-substituted N-alkyl groups, and varying number of methylene bridge groups, have ranges of selectivity towards biological targets that are considered imaging biomarkers in cancer. [34][35][36][37][38][39][40] Resin-supported 3-and 4-arylstannyl intermediates provide an opportunity to produce diverse libraries of radioiodobenzamide precursors to systematically assess structure activity relationships of various biological targets.…”