Nuclear Medicine and Biology 42 (2015) 536–540

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Nuclear Medicine and Biology
journal homepage: www.elsevier.com/locate/nucmedbio

Development of radioiodine-labeled 4-hydroxyphenylcysteamine for
speciﬁc diagnosis of malignant melanoma☆
Masato Kobayashi a,1, Ryuichi Nishii b,⁎, Naoto Shikano c, Leo G. Flores II d, Asuka Mizutani e, Kazuhiro Ogai a,
Jyunko Sugama a, Shigeki Nagamachi b, Keiichi Kawai daWellness Promotion Science Center, Institute of Medical, Pharmaceutical and Health Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa 920-0942, Japan
Department of Radiology, Faculty of Medicine University of Miyazaki, Miyazaki, Japan
Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japand
Department of Cancer Systems Imaging, UT-M.D. Anderson Cancer Center, Houston, TX, USAe
School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japanbca r t i c l e

i n f oArticle history:
Received 20 August 2014
Received in revised form 15 February 2015
Accepted 15 February 2015
Keywords:
Malignant melanoma
Radioiodine
SPECT imaging
Tyrosinase
4-hydroxyphenylcysteaminea b s t r a c t
Introduction: A speciﬁc diagnosis for melanoma is strongly desired because malignant melanoma haspoor prognosis. In a previous study, although radioiodine-125-labeled 4-hydroxyphenyl-L-cysteine( 125I-L-PC) was found to have good substrate afﬁnity for tyrosinase enzyme in the melanin metabolic pathway, 123/131I-L-PC had insufﬁcient substrate afﬁnity for tyrosinase to diagnose melanoma. In this study,
we synthesized 4-hydroxyphenylcysteamine (4-PCA) and developed a novel radioiodine-125-labeled 4hydroxyphenylcysteamine ( 125I-PCA) to increase afﬁnity for the melanin biosynthesis pathway.
Methods: 4-PCA was separated with 2-hydroxyphenylcysteamine (2-PCA), which is an isomer of 4-PCA, and was
examined using melting point, proton nuclear magnetic resonance, mass spectrometry and elemental analysis.
125
I-PCA was prepared using the chloramine-T method under no-carrier added conditions. We performed
biodistribution experiments using B16 melanoma-bearing mice using 125I-PCA, 125I-L-PC, 125I-α-methyl-L-tyrosine,
123
I-m-iodobenzylguanidine and 67Ga-citrate. In vitro assay was performed with B16 melanoma cells, and afﬁnity
for tyrosinase, DNA polymerase and amino acid transport was evaluated using phenylthiourea, thymidine, ouabineand L-tyrosine inhibitor. In addition, partition coefﬁcients of 125I-PCA were evaluated.
Results: In the synthesis of 4-PCA, analysis values did not differ between calculated and reported values, and 4-PCA
was separated from 2-PCA at high purity. In biodistribution experiments, 125I-PCA was accumulated and retained in
B16 melanoma cells when compared with 125I-L-PC. 125I-PCA showed the highest values at 60 min after radiotracer
injection in melanoma-to-muscle ratios, melanoma-to-blood ratios and melanoma-to-skin ratios. Accumulation of
125
I-PCA was signiﬁcantly inhibited by phenylthiourea and thymidine. Partition coefﬁcients of 125I-PCA were lower
than those of N-isopropyl-p-[123I]iodoamphetamine and were not signiﬁcantly different from 125I-L-PC.
Conclusions: 125I-PCA is a better substrate for tyrosinase and DNA polymerase and has higher uptake and longer
retention in B16 melanoma cells when compared with 125I-L-PC. Therefore, 123/131I-PCA has good potential for
diagnosis for malignant melanoma.
Advance in Knowledge: 125I-PCA will be a speciﬁc diagnosis tool for malignant melanoma.
Implications for Patient Care: 123/131I-PCA has good potential for the diagnosis of malignant melanoma whencompared with other SPECT tracers, as well as anti-melanoma chemotherapeutic drugs.
© 2015 Elsevier Inc. All rights reserved.

1. Introduction☆ Financial support: This study was partly funded by Grants-in-Aid for Scientiﬁc Research from the Japan Society for the Promotion of Science (24601008, 24659558) andthe Nakayama Foundation for Human Science.
⁎ Corresponding author at: Department of Radiology, Faculty of Medicine University ofMiyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki-shi, Miyazaki, 889-1692, Japan. Tel.: +81
985 85 2807; fax: +81 985 85 7172.
E-mail addresses: kobayasi@mhs.mp.kanazawa-u.ac.jp (M. Kobayashi),rnishii@med.miyazaki-u.ac.jp (R. Nishii).
1Tel.: +81 76 265 2590; fax: +81 76 265 2590.
http://dx.doi.org/10.1016/j.nucmedbio.2015.02.004
0969-8051/© 2015 Elsevier Inc. All rights reserved.

A speciﬁc diagnosis for malignant melanoma is necessary because it
has such a poor prognosis. Melanoma is caused by elevation of the melanin biosynthesis pathway in melanocytes. Melanoma biosynthesis
comprises conversion of tyrosine to dopa, and then to dopaquinone bytyrosinase oxidation [1].
Sulfur amine derivatives have been developed as anti-melanoma
chemotherapeutic drugs and have high substrate afﬁnity for tyrosinase,which is essential for melanin biosynthesis [2–4]. Chemotherapeutic efﬁcacy has been reported for 4-hydroxyphenyl-L-cysteine (L-PC) [2–6]
and hydroxyphenylcysteamine (PCA) [3–5,7], and their N-acetyl [8,9]M. Kobayashi et al. / Nuclear Medicine and Biology 42 (2015) 536–540

and N-propionyl derivatives [9,10]. These compounds induce toxicity inmalignant melanomas that are positive for tyrosinase. Before starting
chemotherapy, positron emission tomography imaging with 2-[ 18 F]
Fluoro-2-deoxy-D-glucose has recently been applied to detect metastases of melanoma [11]. However, patients cannot undergo PET at all hospitals, as PET is less versatile than SPECT. Although SPECT imaging canbe used to detect metastases of melanoma, speciﬁc SPECT imaging
agents for melanoma have not been developed.
We previously synthesized radioiodine-125-labeled L-PC ( 125I-L-PC)
in order to speciﬁcally diagnose melanoma [12]. Although 125I-L-PC
showed some afﬁnity for tyrosinase, there was insufﬁcient uptake intomelanoma for diagnosis with 123/131I-L-PC. We therefore developed anovel radioiodine-125-labeled 4-PCA ( 125I-PCA) (Fig. 1) to increase
the speciﬁc uptake into melanoma, as compared with 125I-L-PC.
2. Materials and methods
2.1. Synthesis of PCA
We followed the PCA synthesis method of Miura et al. [5]. A mixtureof 28.2 g (300 mmol) of phenol (Nacalai Tesque, Kyoto, Japan) and16.9 g (75 mmol) of cystamine dihydrochloride (Wako, Osaka, Japan)
in 500 ml 47% HBr was reﬂuxed for 2 h in an oil bath. The orange solution was evaporated to dryness in a rotary evaporator. The residue wasdissolved in approximately 100 ml of water, and the solution was adjusted to pH 8.4 with 28% ammonia (Nacalai Tesque), and was thenstirred in a refrigerator for one week. Pale pink needles of pure 2-PCA(1.1% yield) were obtained. The mother liquor of the pH 8.4 mixture
was adjusted to a pH of approximately 10 to give colorless needles ofpure 4-PCA (8.7% yield). The 4-PCA and 2-PCA were analyzed by thinlayer chromatography (TLC) (Merck Millipore, Billerica, MA) witheach sample spotted at 1 μl and methanol/acetate (100/1) used as developing solvent, and was detected by ultraviolet absorption at
254 nm. The structure of 4-PCA was conﬁrmed by determination of proton nuclear magnetic resonance ( 1H-NMR, JEOL JNM-ECS400; Jeol Resonance Inc., Tokyo, Japan), electrospray ionization-mass spectrometry(MS, Shimadzu LCMS-2010A EV; Shimadzu, Kyoko, Japan) and elemental analysis (PerkinElmer 2400; PerkinElmer, Massachusetts). 1H-NMR
data (CD3OD, 400 MHz), δ 2.69–2.72 (t, J = 4.8 Hz, 2H, -CH2-NH2),
2.83–2.86 (t, J = 5.8 Hz, 2H, -S-CH2-), 6.71–6.74 (d, J = 8.8 Hz, 2H, aromatic), 7.26–7.29 (d, J = 9.2 Hz, 2H, aromatic); MS, found MH(+) 170
and calculated MH(+) 170; elemental analysis, calculated for
C8H11NOS: C, 56.78, H, 6.55, N, 8.28, S, 18.94 and found for C, 56.41, H,
6.50, N, 8.41, S, 19.03 and melting point 116-119 °C. These data werecompared with previously reported values [2,5].
2.2. 125I- and 127I-labeled 4-PCA
125

I-PCA was prepared by the chloramine-T method under nocarrier added conditions [12]. Brieﬂy, 0.33 mM chloramine-T (Nacalai
Tesque) at a concentration of 1.0 × 10-8 mol in 0.05 M phosphate buffer(pH 6.2) was added to a mixture of 4-PCA (0.1 μ mol) in 0.5 mM phosphoric acid (pH 6.2) and no-carrier added 37 MBq Na125I (Perkin Elmer,

Fig. 1. Structure of 125I-PCA.

537

Waltham, MA) in 0.4 M phosphate buffer (pH 8.5). Five minutes later,
10 nmol of sodium metabisulﬁte in 0.05 M phosphate buffer (pH 6.2)
was added to stop the reaction. Labeling efﬁciency was examined by
TLC with a solvent system of methanol/acetic acid (100/1). 125I-PCA
was puriﬁed by high performance liquid chromatography (HPLC)
using a C18-MS-II column (Nacalai Tesque) with 85% methanol and
15% acetic acid as eluent at a ﬂow rate of 0.5 ml/min. The structureof I-PCA was conﬁrmed by NaI-127 (Nacalai Tesque) labeled PCA(127I-PCA). 127I-PCA was also synthesized using the same labeling method and HPLC method as for 125I-PCA. Brieﬂy, 0.33 mM chloramine-T(Nacalai Tesque) in 0.05 M phosphate buffer (pH 6.2) was added to a
mixture of 10 μmol 4-PCA in 0.5 mM phosphoric acid (pH 6.2) and
0.33 mmol Na 127I in 0.4 M phosphate buffer (pH 8.5). One hour later,
10 nmol of sodium metabisulﬁte in 0.05 M phosphate buffer (pH 6.2)
was added to stop the reaction. Using the same procedures with 1HNMR and MS for identiﬁcation of 4-PCA, the 1H-NMR data (CD3OD,
400 MHz) were δ 2.72–2.75 (t, J = 5.0 Hz, 2H, -CH2-NH2), 2.86–2.89(t, J = 6.0 Hz, 2H, -S-CH2-), 6.74–6.77 (d, J = 8.6 Hz, 2H, aromatic)
and 7.16–7.19 (d, J = 9.0 Hz, 1H, aromatic) and MS data revealed an
MH(+) of 296 and a calculated MH(+) of 296 for C8H10INOS.
2.3. Melanoma cells
At 37 °C and under 5% CO, B16 melanoma cells (Riken Cell Bank,
Ibaraki, Japan) were incubated in Dulbecco's Modiﬁed Eagle Medium(DMEM; Sigma-Aldrich, St. Louis, MO) including 10% fetal calf serum(Dainippon Sumitomo, Osaka, Japan).
2.4. Biodistribution in B16 melanoma-bearing mice
Animal studies were approved by the Animal Care Committee atKanazawa University and were conducted in accordance with the international standards for animal welfare and institutional guidelines. We
prepared melanoma cells at 5 × 10 6 cells per 100 μl and injected themsubcutaneously into the right thigh of 6-week-old C57BL6 male mice
(SLC Inc., Hamamatsu, Japan). Mice were housed for about ten days
under a 12-h light/12-h dark cycle with free access to food and water.
Mice were fasted with no food overnight with water supplied ad libitum
before experiments. At about ten days later, the size of the melanoma became palpable, and 37 kBq 125I-PCA, 125I-3-Iodo-α-methyl-L-tyrosine(125I-AMT) [13,14] or 123I-m-iodobenzylguanidine (123I-MIBG) (Fujiﬁlm
RI Pharma Co., Ltd., Tokyo, Japan) [15], 67Ga-citrate (Fujiﬁlm RI PharmaCo., Ltd., Tokyo, Japan) [14] was injected via the tail vein in ﬁve tumorbearing mice. Mice were sacriﬁced at 5, 15, 30, 60 and 120 min postinjection. After blood was sampled via cardiocentesis, brain, pancreas, spleen,
stomach, intestine, kidney, liver, heart, lung, skin muscle and melanoma
were excised. Radioactivity in weighed tissue samples was measured
using a gamma counter (ARC-380; Aloka, Tokyo, Japan). Data areexpressed in terms of injected dose (%ID/organ) for stomach and intestineand injected dose per g wet tissue (%ID/g tissue).
2.5. In vitro assay with B16 melanoma cells
Transport assays were performed using the methods of Nishii et al.
and Kobayashi et al., with some modiﬁcations [12,16]. Brieﬂy, B16
melanoma cells were seeded onto 24-well cell culture multiwell plates
at a density of 5 × 10 5 cells/ml/well. Assays were conducted at 24 hafter seeding. After culture medium was removed, each well was incubated with 1 ml of HEPES buffer (pH 7.4) for 10 min at 37 °C. Cells
were then incubated with 0.5 ml of incubation medium containing
18.5 kBq 125I-PCA for 30 min at 37 °C (control conditions). Inhibition
studies of tyrosinase, DNA polymerase and membrane active transport
were carried out using 0.5 mM phenylthiourea (Sigma, St. Louis, MO),
0.5 mM thymidine (Nacalai Tesque), 0.5 mM ouabine (Sigma) and1 mM L-tyrosine (Sigma), respectively. B16 melanoma cells were incubated for 30 min using 125I-PCA and these inhibitors. At the end of538

M. Kobayashi et al. / Nuclear Medicine and Biology 42 (2015) 536–540

Table 1
Biodistribution of 125I-PCA in B16 melanoma-bearing C57BL6 mice.
Organ or tumor

Time (min)

Blood
Brain
Pancreas
SpleenStomach⁎Intestine⁎
Kidney
Liver
Heart
Lung
Skin
MuscleMelanoma

5

15

30

60

120

5.52 ± 1.06
1.89 ± 0.15
11.38 ± 3.26
7.99 ± 2.68
0.49 ± 0.15
6.82 ± 1.76
33.30 ± 1.91
24.04 ± 3.77
6.25 ± 0.17
23.63 ± 3.35
3.11 ± 0.47
3.22 ± 0.31
3.12 ± 0.72

4.07 ± 0.19
1.58 ± 0.17
4.53 ± 0.75
3.50 ± 0.38
0.55 ± 0.16
8.15 ± 2.22
17.78 ± 2.71
12.47 ± 2.38
2.93 ± 0.49
18.01 ± 2.44
1.84 ± 0.33
1.57 ± 0.42
3.26 ± 1.03

2.53 ± 0.43
1.16 ± 0.10
2.37 ± 0.54
1.99 ± 0.78
0.75 ± 0.31
9.33 ± 1.65
9.80 ± 1.31
6.21 ± 0.84
1.60 ± 0.23
13.61 ± 1.40
1.34 ± 0.24
0.85 ± 0.12
3.66 ± 0.86

1.56 ± 0.05
0.45 ± 0.08
0.74 ± 0.16
1.08 ± 0.45
0.77 ± 0.25
12.77 ± 2.73
3.83 ± 1.38
2.24 ± 0.86
0.76 ± 0.34
7.02 ± 0.59
0.52 ± 0.13
0.31 ± 0.09
3.44 ± 0.43

0.46 ± 0.07
0.21 ± 0.08
0.25 ± 0.15
0.28 ± 0.07
0.53 ± 0.19
16.48 ± 2.92
1.28 ± 0.47
1.36 ± 0.42
0.32 ± 0.11
2.20 ± 0.83
0.45 ± 0.05
0.17 ± 0.07
3.25 ± 0.43

Percent injected dose per g tissue (%ID/g), mean ± standard deviation of data from ﬁve mice.
⁎ %ID/organ calculated from %ID/g and measured organ weights.

incubation, each well was rapidly washed twice with 1 ml of ice-cold incubation medium. Cells were then solubilized in 0.5 ml of 0.1 N NaOH,
and radioactivity was measured with a liquid scintillation counter(LSC-5100; Aloka, Tokyo, Japan). Subsequently, cells were detachedfrom one another with trypsin to facilitate further counting. All experimental conditions were examined in quadruplicate assays.

Partition coefﬁcients of 125I-PCA were measured using 2.0 ml of noctanol as the organic phase and 2.0 ml of 0.1 M phosphate buffer(pH 7.0 for tumor tissue and pH 7.4 for plasma) as the aqueous phase.
The n-octanol and buffer were pre-mixed twice using a mechanical

b
3.0

14.0

2.5

12.0

Melanoma-to-muscle ratio

Melanoma-to-blood ratioa2.6. Partition coefﬁcients

2.0
1.5
1.0
0.5
0.0

10.0
8.0
6.0
4.0
2.0
0.0

5 min

15 min60 min

5 min

15 minTime after injection

60 minTime after injectionc8.0

Melanoma-to-skin ratio

7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
5 min

15 min60 minTime after injection
125 I-PCA

125 I-L-PC

125

I-AMT

123

I-MIBG

67

Ga-citrate

Fig. 2. Melanoma-to-blood ratios (a), melanoma-to-muscle ratios (b) and melanoma-to-skin ratios (c) in B16 tumor-bearing C57BL6 mice at 5, 15 and 60 min after injection. 125I-PCA
increased gradually after injection and showed higher values than other radiotracers at 60 min after injection for all ratios.

M. Kobayashi et al. / Nuclear Medicine and Biology 42 (2015) 536–540

3.4. In vitro assay in B16 melanoma cells

Table 2
In vitro assay in B16 melanoma cells using inhibitors.
% of control
Inhibitors

Phenylthiourea

Thymidine

OuabineL-tyrosine

125

38.4 ± 11.8⁎⁎
55.2 ± 12.3⁎
84.8 ± 5.4

11.5 ± 3.6⁎⁎
68.4 ± 12.1⁎
88.9 ± 18.2

102.2 ± 19.5
113.7 ± 15.8
72.6 ± 0.9

90.3 ± 10.3
77.6 ± 14.9
58.3 ± 2.5⁎

I-PCA
125
I-L-PC123
I-AMT

As shown in Table 2, accumulation of 125I-PCA and 125I-L-PC wassigniﬁcantly inhibited by phenylthiourea and thymidine, but was notinhibited by ouabine and L-tyrosine. The inﬂuence of 125I-PCA on
phenylthiourea and thymidine was greater than that of 125I-L-PC.
3.5. Partition coefﬁcients⁎ P b 0.05.
⁎⁎ P b 0.01 vs. control.

mixer for 1 min at room temperature. Then, 20 μl of 125I-PCA in saline
was added and mixed twice for 1 min at room temperature. The
radioactivity of 200 μl of each phase was measured using a gamma
counter after centrifugation. As reference, the partition coefﬁcientsof 125I-L-PC, 123I-AMT and N-isopropyl-p-[ 123I]iodoamphetamine(123I-IMP) were used [12,13].
2.7. Statistical analysis
Data are presented as means and standard deviation (SD). P values
were calculated using a two-tailed paired Student's t-test for comparison between two groups. P values of less than 0.01 or 0.05 were considered to be signiﬁcant.
3. Results
3.1. Synthesis of 4-PCA
On TLC analysis, Rf values of 4-PCA, cystamine and phenol were respectively 0.50–0.60, 0.10–0.20 and 0.65–0.75 in methanol and acetate(100:1). The yield of 4-PCA was 8.7%.
3.2. Radiosynthesis of 125I-PCA
On TLC analysis, Rf values of 125I-PCA and 125I - were respectively
0.40–0.50 and 0.75–0.85. The labeling efﬁciency of 125I-PCA was morethan 73%. On HPLC analysis, retention times were about 5 min for 125I, 30 min for unlabelled 4-PCA, and 40 min for 125I-PCA. After puriﬁcation, no-carrier added 125I-PCA was greater than 95% pure and separated from unlabeled 4-PCA.
3.3. Biodistribution in B16 melanoma-bearing mice
125

I-PCA peaked in B16 melanoma cells at 30 min after injection andhigher values in B16 melanoma cells were seen when compared withblood, and these levels were retained in B16 melanoma cells beyond
30 min after injection (Table 1). In normal tissues, higher uptakeof 125I-PCA was observed in the kidney, liver and lung at 5 minafter injection, but 125I-PCA was quickly washed out. Radioactivity
in blood also disappeared quickly, and in the stomach, it did not
subsequently increase. Fig. 2 shows the melanoma-to-blood
ratios, melanoma-to-muscle ratios and melanoma-to-skin ratios using
125
I-PCA, 125I-L-PC, 125I-AMT, 123I-MIBG and 67Ga-citrate at 5, 15 and60 min after injection. 125I-PCA showed the highest ratios of allradiotracers after 60 min of injection.

pH

7.0

7.4

125

−0.34 ± 0.05
−0.28 ± 0.04
−0.88 ± 0.00
0.72 ± 0.03

−0.43 ± 0.03
−0.37 ± 0.04
−0.91 ± 0.00
0.94 ± 0.01

Log (n-octanol/0.1 M phosphate buffer).

Partition coefﬁcients of 125I-PCA were not signiﬁcantly different
from 125I-L-PC, but were greater than those of 123I-AMT and lower
than those of 123I-IMP (Table 3).
4. Discussion
In this study, 125I-PCA accumulated in and was retained bymalignant melanoma cells (Table 1). Tyrosine analogues, which aretyrosinase substrates, are good candidates for developing drugs formelanoma-targeting chemotherapies [17]. 4-PCA is a better substrate
for tyrosinase than 2-PCA because the structure of 4-PCA is more similar
to tyrosine than 2-PCA [3,5,18]. Miura et al. showed that the afﬁnity of
4-PCA, a precursor of 125I-PCA, was higher than that of L-PC [5]. As
shown in Table 2, 125I-PCA has a greater afﬁnity for tyrosinase inmelanocytes than 125I-L-PC, as radioactivity of 125I-PCA was signiﬁcantly inhibited by phenylthiourea, which is an inhibitor of tyrosinase, andthymidine, which is a DNA polymerase inhibitor, as compared with
125
I-L-PC. Yamada et al. reported that 4-PCA for chemotherapy isoxidized by tyrosinase to the o-quinone form via the catechol derivative,
and that some of the quinones then conjugate with sulfhydryl enzymes,
including DNA polymerase [7]. Meristem cells incorporate thymidine
and then complete DNA replication before cell division. However,there was no cell accumulation of 125I-PCA through the amino acidtransporter. Accumulation of 125I-AMT was inhibited by ouabine andL-tyrosine, but was not inhibited by phenylthiourea and thymidine. In
addition, the lipophilicity of 125I-PCA was markedly lower than that of123
I-IMP, has high cell transportation by high lipophilicity (Table 3).
Therefore, 125I-PCA accumulated in melanoma cells due to its highafﬁnity for both tyrosinase and DNA polymerase.
In B16 melanoma-bearing mice (Table 1), 125I-PCA accumulated inmelanoma and was retained after 30 min of injection. 125I-PCA
showed faster washout from blood and was quickly excreted by the kidney. 125I-PCA also accumulated in normal tissues such as the pancreas
and lung when compared to 125I-L-PC [12], but was excreted quickly
from normal tissues. With regard to stability of 125I-PCA, radioactivity
in the stomach typically increases if radioiodine-labeled tracers undergo
deiodination. As shown in Table 1, radioactivity did not increase. Therefore, in vivo stability of 125I-PCA is estimated to be higher. It is importantfor SPECT imaging to improve melanoma-to-blood ratios, melanomato-muscle ratios and melanoma-to-skin ratios. For all ratios, 125I-PCA increased gradually after injection and showed peak values at 60 min after
injection, as compared with other SPECT tracers that are able to detectmelanoma (Fig. 2). Thus, 125I-PCA is an effective imaging radiotracer
for malignant melanoma.
5. Conclusion
125
I-PCA is a better substrate for tyrosinase and DNA polymerase andhas higher uptake and longer retention in malignant melanoma cells
when compared with 125I-L-PC. Therefore, 123/131I-PCA has good potential for diagnosis for malignant melanoma.

Table 3
Partition coefﬁcients at pH 7.0 and 7.4.

I-PCA
125
I-L-PC
123
I-AMT
123
I-IMP

539

Acknowledgments
The author would like to thank Noriko Mizukami, Kyoko
Nishimura and the other laboratory staff of Kanazawa University
and Miyazaki University.

540

M. Kobayashi et al. / Nuclear Medicine and Biology 42 (2015) 536–540

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