Synthesis of a new 18F labeled porphyrin for potential application in positron emission tomography. in vivo imaging and cellular uptake

Article abstract of DOI:10.1039/c5ra16103g

Herein we report, for the first time, the development, labeling optimization and preliminary biodistribution studies of an [¹⁸F] radiolabeled meso-tetraphenylporphyrin. After synthesis and characterization of the "cold" fluorinated porphyrin, the conditions have been transferred to an automated radiochemistry module and the desired 5-(2-[¹⁸F]fluoroethoxyphenyl)-10,15,20-triphenylporphyrin was prepared in a radiochemical purity >95%. Moreover, data regarding the uptake into human bladder tumor cells and the radiotracer biodistribution after C57BL/6 mice injection are also presented. The maximum cellular uptake was reached at 45 min and was of 2.5%.

Full text of DOI:10.1039/c5ra16103g

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ARTICLE
Synthesis of a New 18F Labeled Porphyrin for Potential
Application in Positron Emission Tomography. In vivo
Imaging and Cellular Uptake
Received 00th January 20xx,
Accepted 00th January 20xx
Ana V. C. Simões,a Sara M. A. Pinto,a Mário J. F. Calvete,a* Célia M. F. Gomes,b,c Nuno C. Ferreira,c,d
DOI: 10.1039/x0xx00000x
Miguel Castelo-Branco c,d Jordi Llop,e Mariette M. Pereiraa* and Antero J. Abrunhosac,d
*
www.rsc.org/
Herein we report, for the first time, the development, labeling optimization and preliminary biodistribution studies of a
18F] radiolabeled meso-tetraphenylporphyrin. After synthesis and characterization of the “cold” fluorinated porphyrin, the
[
conditions have been transferred to an automated radiochemistry module and the desired 5-(2-[18F]fluoroethoxyphenyl)-
10,15,20-triphenylporphyrin was prepared in a radiochemical purity >95%. Moreover, data regarding the uptake into
human bladder tumor cells and the radiotracer biodistribution after C57BL/6 mice injection is also presented. The
maximum cellular uptake was reached at 45 min and was of 2.5%.
radiotracer outside of the production centre.11 Furthermore,
albeit the myriad of applications possible for tetrapyrrolic
macrocycles,12 and particularly their ability for accumulation in
1. Introduction
It is widely accepted today that the best way to diminish the
worldwide mortality caused by cancer (>20.000 per day) is the
development of methods for early stage cancer detection,
particularly using efficient and economical non-invasive
imaging techniques.1 Some of the most important imaging
techniques used for cancer diagnosis are: magnetic resonance
imaging (MRI)2,3 single photon emission tomography (SPECT)4,5
and positron emission tomography (PET).6,7 PET is a nuclear
imaging technique that combines high sensitivity and accurate
image quantification allowing the visualization in vivo of
chemical processes in organs and tissues that can help the
diagnosis of important pathologies. In recent years this
technique has also found an increasing application in the
development of new drugs by providing critical information
regarding in vivo distribution, mechanism of action and
kinetics of candidate compounds.8,9
The most commonly used radionuclides for PET are [14O], [13N],
[11C], [64Cu], [68Ga] and [18F].10 Among them the most widely
used, by far, is [18F], since, contrarily to the complexation of
labeled metals, the labeling with [18F] atoms does not
significantly alter the biological properties of the molecules
and its moderate t1/2 (109.8 min) permits an adequate time for
synthetic and imaging processes, allowing its application as a
tumor cells for PDT treatment,13,14,15 up to now, there are only
a few examples in the scientific literature of contrast agents
incorporating tetrapyrrolic macrocycles for PET imaging.16
Recently, our group6 presented the optimization of reaction
conditions to promote monomethylation of 5,10,15,20-
tetrakis(3-hydroxyphenyl)porphyrin with CH3I at minute time
scale and the syntheses of the corresponding labeled
porphyrin using short-lived carbon-11, prepared in the
automated radiolabeling system. The [11C] labeled porphyrin
was obtained with high radiochemical purity and specific
radioactivity and biodistribution studies were made using PET
imaging. Other authors17 reported the synthesis of [64Cu]-
5,10,15,20-tetrakis(pentafluorophenyl)porphyrin, through the
reaction of freshly prepared [64Cu]CuCl2 with the former,
obtaining 97% radiochemical purity with a specific activity of
14-16 GBq/mmol. However, in the scientific literature, there
are very few reports on the labeling of tetrapyrrolic
macrocycles with [18F]. For instance, the synthesis of 5-(4-
[18F]fluoro-phenyl)-10,15,20-tris(3-methoxyphenyl)porphyrin
has
been
reported,18
where
radiolabeled
4-
[18F]fluorobenzaldehyde was used as starting material and,
more recently, other researchers19 published a different
approach for the direct [18F]-labeling using [18F] fluoride ion
trough nucleophilic substitution reactions with properly
substituted zinc porphyrins, with radiochemical yields lower
than 10%. Nevertheless, it should be emphasized that none of
the reported studies on [18F] labeling presented any
biodistribution studies of the radiolabeled compounds.
a.CQC, Department of Chemistry, Rua Larga, 3004-535 Coimbra, Portugal. E-mail:
mcalvete@qui.uc.pt Tel: +351239854474.
b.Pharmacology and Experimental Therapeutics, IBILI - Faculty of Medicine,
University of Coimbra, Coimbra, Portugal
CNC-IBILI Consortium, University of Coimbra, Coimbra, Portugal. E-mail:
c
antero@pet.uc.pt
Herein we describe for the first time the development, labeling
and biodistribution studies of a [18F] radiolabeled meso-
d
Institute for Nuclear Sciences Applied to Health (ICNAS), University of Coimbra,
Coimbra, Portugal.
CICbiomaGUNE, San Sebastián, Spain.
e
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tetraphenylporphyrin. After synthesis and characterization of previously described by our group,21 which involves the use of
the “cold” fluorinated porphyrin, we have proceeded to the a Al-zeolite as Lewis catalyst in the synthesis of hindered
synthesis of the desired 5-(2-[18F]fluoroethoxyphenyl)- halogenated meso-phenyl porphyrins. Therefore, in a typical
10,15,20-triphenylporphyrin
using
an
automated reaction, 3 molar equivalents of benzaldehyde, 1 molar
radiochemistry module. The complete process including equivalent of 4-hydroxybenzaldehyde, 4 molar equivalents of
purification and quality control using HPLC is described. pyrrole mixed in glacial acetic acid and nitrobenzene (7:5), in a
Moreover, data regarding the uptake into human bladder 0.42 molar concentration, and 0.016 molar equivalents of NaY
tumor cells and the radiotracer biodistribution after C57BL/6 were used.22 The reaction mixture was heated at 130ºC for 2
mice injection is also is also presented.
hours and
1
was obtained, after workup, in 16% yield (Scheme
was reacted with 1,2-diyl bis(4-
1,
a). Then, porphyrin 1
methylbenzenosulfonate)ethane, which was previously
prepared according to literature prtocedures,23 using Cs2CO3 as
2. Results and Discussion
base, yielding 48% of monotosylated porphyrin
).
3 (Scheme 1,
2.1. “Cold” synthesis of fluorinated porphyrin 4
b
The
synthesis
of
5-(4-hydroxyphenyl)-10,15,20-
triphenylporphyrin (
1)
20 was carried out using the NaY method,
Scheme 1. “Cold” synthesis of porphyrin 4.
conditions, the nucleophilic substitution reaction was optimized
with two different fluorinating agents, namely tetraꢀ
Table 1 - Reaction conditions for “cold” fluorination of
porphyrin 3
nꢀ
butylammonium fluoride (TBAF) and cesium fluoride (CsF),
using acetonitrile (CH3CN) as solvent in all experiments (Table
Fluorinating
agents
T
Reaction time
(h)
Yield of 4
(%)
Entry
1
(ºC)
1
From Table 1, we can assume that the best conditions to
).
70
11h
59
CsF
2
3
80
90
8h
6h
62
63
promote the nucleophilic substitution reaction using
compound
3 involves the use of TBAF as fluorinating agent,
4
5
6
70
80
90
2h
1h
1h
80
80
87
since reactions using this agent (entries 4-7, Table 1) reached
yields of 80%-90%, significantly higher than the ones obtained
using CsF as fluorinating agent (entries 1-3, Table 1).
TBAF
7
90
0.5 h
85
Moreover, while a one hour reaction time at 90 ºC produced a
yield of 87% (entry 6, Table 1), the substitution reaction
carried out, at the same temperature, in 30 minutes yielded
In order to check the “cold” fluorination of porphyrin
3, to
obtain fluorinated porphyrin
4 (Scheme 1, c), under laboratorial
compound
4
in 85% yield (entry 7, Table 1). Since the reaction
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time is a crucial aspect for optimizing the conditions for using Kryptofix222 and K2CO3 in a conical vial and azeotropically
preparing a suitable [18F] radiotracer (t1/2 [18F] =109.8 min), we removing water with acetonitrile in a stream of nitrogen.
decided that these were the optimal conditions for Finally, the dried [18F]KF was placed into anhydrous CH3CN,
preparation of compound
4. So, in a typical experiment, the followed by the addition of a solution of porphyrin 3 in CH3CN.
porphyrin 3 was dissolved in CH3CN, after which a THF solution Then, the solution was sealed and kept at 100ºC for 25 min
of TBAF was added. The reaction mixture was left to react at
90 ºC for 30 min. After workup the desired fluorinated
(Scheme 2).
porphyrin 4 (Scheme 1, c) was obtained in 85% yield.
In order to acquire the purity and efficiency of the nucleophilic
substitution reaction, HPLC apparatus equipped with an
analytical column was used to optimize the separation
conditions of porphyrins
depicted in Figure 1
3
and
4, using the HPLC conditions
.
UVꢀVis Detector.
λ=420nm
3
4
Scheme 2. Synthesis of fluoro-labeled porphyrin 4[18F].
Fig. 1. HPLC chromatograms of porphyrins 3 and 4. Conditions: 98% methanol: 2%
Quality control of the mixture was performed in a HPLC
apparatus, equipped with an analytical column, UV-Vis
detector and activity detector, using the conditions previously
obtained for the corresponding non-labeled fluorinated
porphyrin (Figure 3).
ammonium formate buffer 0,1 M (pH=7.2) and 1 mL/min flux.
Optimization of separation conditions gave a retention time of
5-6 min for 3, while for fluorinated porphyrin 4 a retention
time of 7-8 min was achieved. Moreover, the conditions for
HPLC separation using a semi-preparative column were also
optimized. In this case, in optimum conditions, the retention
UVꢀVis Detector.
λ=420nm
3
time of
3 was 9-10 min (550-650 s) and for 4 a retention time
of 13-14 min (800-900 s) was achieved (Figure 2).
Activity detector
18F-]
UVꢀVis Detector
λ=273nm
[
36a
3
Fig. 3. HPLC chromatogram the reaction mixture after radiolabelling with [
18F].
Conditions: 98% methanol: 2% ammonium formate buffer 0,1 M (pH=7,2) and flux of
1mL/min.
4
Through the analysis of the HPLC chromatogram it is possible
to attribute the peak at 5-6 min (UV-Vis detector) to the
starting material (3) and a peak at around 8 min to the labeled
fluorinated porphyrin [18F]
chromatogram, using the activity detector, shows a peak at 8
minutes attributed to the labeled porphyrin [18F]
and
-4.
In addition, the HPLC
Fig. 2. HPLC chromatogram of porphyrins 3 and 4, obtained using a semi-preparative
column. Conditions: 98% methanol: 2% ammonium formate buffer 0,1 M (pH=7.2) and
flux of 8 mL/min.
-
4
another peak at around 2minutes corresponding to unreacted
[18F-] anion. The radiochemical yield was 31.0 ± 15.8% (n=4).
Subsequently, the reaction mixture was purified using an HPLC
equipped with the same semi-preparative column under the
optimized conditions previously described for the "cold" 5-(2-
fluoroethoxyphenyl)-10,15,20-triphenylporphyrin. The fraction
corresponding to the labeled porphyrin (showing activity
between 10-11 min) (Figure 4) was collected and re-submitted
to quality control to confirm the purity of 5-(2-
2.2. [18F] radiolabeling: Synthesis of porphyrin [18F]-4
Once checked the “cold” conditions for the synthesis of the
fluorinated meso-tetraphenyl substituted porphyrin, the
reaction was translated to an automated radiosynthesis
process. A modification of the standard Hamacher method was
used.24 Aqueous [18F]fluoride was produced by the irradiation
of H218O via the 18O(p,n)18F nuclear reaction in a cyclotron.
Resolubilization of the aqueous [18F]fluoride was accomplished
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[18F]fluoroethoxyphenyl)- 10,15,20-triphenylporphyrin (Figure Cells were incubated with the compound at 37ºC during 60
7)
.
min. At different time-points, samples were collected and the
radioactivity of the pellet and supernatant was measured with
a radioisotope calibrator well counter within the 18F sensitivity
energy window of 400-600 keV. The results were expressed as
the percentage of cell radioactivity associated to the total
radioactivity added and normalized per million of cells. The
cellular uptake of the compound increased progressively along
the first 45 minutes and then started to decline (Figure 6). The
maximum cellular uptake was reached at 45 min and was of
2.5%.
2.4. Exploratory in vivo PET imaging and biodistribution
Fig. 4. Chromatogram obtained during purification of ([18F]-4) reaction mixture, using a
Evaluation of in vivo biodistribution was achieved using normal
mice (C57BL/6 mice). The animals were injected at the tail vein
with 500 and 900kBq of 5-(2-[18F]fluoroethoxyphenyl)-
semi-preparative HPLC.
UVꢀVis detector
λ=420nm
10,15,20-triphenylporphyrin ([18F]
resolution imaging system. PET planar images of whole body
were acquired at 45 minutes Figure and rapid
-4) and placed on a high
(
7
)
a
biodistribution, with low uptake in brain, pulmonary and
muscle tissues were observed. Uptake in the liver is clearly
visible, demonstrating that this is the main pathway for
excretion of the compound.
Activity Detector
Fig. 5. Chromatogram obtained after purification of [18F]-4 mixture using an HPLC
equipped with an analytical column. Conditions: 98% methanol: 2% ammonium
formate buffer 0.1 M (pH=7,2) and flux of 1mL/min.
A)
B)
From the analysis of Figure 5 we observe, both by UV-Vis and
activity detection, a single peak at ca 8 min, as previously
observed in the cold conditions (Figure 3) which corroborates
the efficient radiosynthesis of porphyrin [18F]
-
4
. Therefore, it Fig. 7. Micro-PET studies on normal mice injected with 500kBq (A) and 900kBq (B) of 5-
(2-[18F]fluoroethoxyphenyl)-10,15,20-triphenylporphyrin ([18F]-4). Whole body images
should be emphasized that both labeling and purification of
porphyrin [18F] with radioactive 18F were successfully
-4
were acquired at 45 min. and are normalized for injected activity.
accomplished, since the radiolabeled porphyrin was obtained
in a radiochemical purity >95%. Specific activity was in the
range of 2-7 – 3.2 Ci/µmol.
3. Conclusions
In summary, we have successfully developed and optimized
2.3. Tumor cell radiotracer uptake
the
conditions
for
labeling
meso-substituted
tetraphenylporphyrin derivative with [18F]. After synthesis and
characterization of the corresponding “cold” fluorinated
porphyrin, the desired 5-(2-[18F]fluoroethoxyphenyl)-10,15,20-
triphenylporphyrin was prepared in an automated
radiochemistry module with radiochemical purity >95%.
Moreover, data regarding the uptake into human bladder
tumor cells and the radiotracer biodistribution after C57BL/6
mice injection is also is also presented. The maximum cellular
uptake was reached at 45 min and was of 2.5%. Rapid
biodistribution, with low uptake in brain, pulmonary and
muscle tissues were observed. Uptake in the liver was clearly
visible, demonstrating that this is the main pathway for
excretion of the compound. Further studies on the
improvement on biodistribution and cellular uptake of this
type of compounds are needed, and are currently undergoing.
Cellular uptake of 5-(2-[18F]fluoroethoxyphenyl)-10,15,20-
triphenylporphyrin ([18F]
-4) was carried out in a human
bladder cancer cell line (UM-UC3).
Fig. 6. Uptake studies of 5-(2-[18F]fluoroethoxyphenyl)-10,15,20 triphenylporphyrin
([18F]-4) in a human bladder tumor cell line (UM-UC3). (A) Results are reported as the
percentage of cell radioactivity associated with the total radioactivity added and
normalized per million of cells; (B) Total counts in the pellet and supernatant.
4. Experimental
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4.1. General considerations
evaporated to dryness and the resulting solid dried under
vacuum and weighed to give 60 mg (0.0938 mmol) of (16%
1
Commercially available reagents were purchased from Aldrich,
Fluorochem and Acros, being used as received. All solvents
were pre-dried according to standard laboratory techniques.
1H NMR spectra were recorded on a 400 MHz Brucker-Amx.
The chemical shifts are given in parts per million (ppm) relative
to tetramethylsilane at δ 0.00 ppm for proton spectra. 19F NMR
spectra were recorded on a 376.5MHz Brucker-AmxMass,
using TFA (δ= -76.2 ppm) as reference. Mass spectra were
acquired using an Applied Biosystems Voyager DE-STR
instrument equipped with a nitrogen laser (λ = 337 nm) or
yield). Characterization data is in accordance with the
literature.25
4.2.2. 1,2-Diyl bis(4-methylbenzenosulfonate)-ethane (2)
To a solution of ethylene glycol (0.3 mL, 5 mmol) and
triethylamine (0.9 mL, 6 mmol) in anhydrous CH2Cl2 (30 mL),
tosyl chloride (230 mg, 1.25 mmol) dissolved in 100 mL of
CH2Cl2 was slowly added. The reaction mixture was stirred at
room temperature in inert for 24 h. Subsequently
ethanolamine (6 mL) was added to react with the excess of
tosyl chloride and the resulting mixture was washed with
water (200 mL) and extracted with CH2Cl2. The organic phase
was washed with a solution of HCl 1M and brine. After
evaporation under reduce pressure the obtained solid was
Bruker microTOFQ instrument by Unidade de Masas
e
Proteomica – Universidade de Santiago de Compostela, Spain.
Column chromatographies were performed with silica gel
grade 60, 70-230 mesh as stationary phase.
Radiolabelling with [18F]fluoride was performed at Institute for
Nuclear Sciences Applied to Health (ICNAS, University of
Coimbra), equipped with an CYCLONE 18/9 cyclotron (IBA.
Louvain-la-Neuve, Belgium) and an automated synthesis
module (IBA Synthera). Analytical control of the labeling
reaction was performed in HLPC Agilent Technologies 1200
series, with an UV-Visible detector Agilent Technologies 1200
series with an activity detector Raytest Gabi Star and a
chromatographic column Halo C18, 5 µm, 4.6×100mm.
recrystallized using ethanol, giving
Characterization data is in accordance with the literature.23
1H NMR (400 MHz, CDCl3):
, ppm 7.73 (d, J=8.1Hz, 4H, Ar-H),
2
in 48% yield.
δ
7.34 (d, J=8.2Hz, 4H, Ar-H), 4.18 (s, 4H, -CH2), 2.45 (s, 6H, CH3).
HRMS-ESI-TOF [M+Na]+- m/z 393.0433 calcd. [C16H18NaO6S2]
393.0437.
4.2.3. 5-(2-Tosylethoxyphenyl)-10,15,20-triphenylporphyrin (3)
5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (63 mg, 0.1
mmol),
2 (392 mg, 1 mmol) and Cs2CO3 (162 mg, 0.5 mmol)
were dissolved in 10 mL of CH3CN. The reaction mixture was
stirred at 80 ºC for 24 h. After solvent evaporation, the
resulting solid was re-dissolved in CH2Cl2 and washed with
water, a sodium bicarbonate solution and brine. The organic
phase was evaporated and the resulting product was purified
by silica gel column chromatography using CH2Cl2 as eluent,
All animal experiments were performed by certified persons
(holders of FELASA type C and DGV certificates) according to
ethics committee recommendations and approval by the
animal research committee of University of Coimbra and
Portuguese animal welfare regulation. The researchers always
took in consideration the animal suffering and implemented
the 3R rule. The experimental procedure used conforms to the
European Convention for the Protection of Vertebrate Animals
used for Experimental and other Scientific Purposes (ETS No.
123) and to the Guide for the Care and Use of Laboratory
Animals published by the US National Institutes of Health
(DHEW Publication No. (NIH) 82–23, Revised 1996, Office of
Science and Health Reports, DRR/NIH, Bethesda, MD 20205).
yielding the porphyrin
3 as a dark violet amorphous solid (m.p.
> 300 ºC), in 48% yield.
UV-vis (toluene): λmax, nm (ε, M-1∙cm-1) 420 (3.5x105), 515
(2.3x104), 546 (6.2x103), 591 (6.9x103), 656 (4.3x103). 1H NMR
(400 MHz, CDCl3): δ, ppm 8.85 (s, 8H, β-H), 8.22 (d, J=6.3Hz,
6H, Ar-H), 8.09 (d, J=8.3Hz, 2H, Ar-H), 7.95 (d, J=8.1Hz 2H, Ar-
H), 7.79-7.74 (m, 6H, Ar–H + 3H, Ar-H), 7.43 (d, J=8.0Hz, 2H, Ar-
H), 7.15 (d, J=8.3Hz, 2H, Ar-H), 4.56 (t, J=4.0Hz, 2H, -CH2-), 4.43
(t, J=4.0Hz, 2H, -CH2-), 2.48 (s, 3H, CH3), -2.76 (s, 2H, NH).
HRMS-ESI-TOF [M+H]+. m/z 829.2827 calcd. [C53H41N4O4S]
829.2843.
4.2. Synthesis
4.2.1. 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (1)
4.2.4. 5-(2-Fluoroethoxyphenyl)-10,15,20-triphenylporphyrin
The zeolite NaY (1.0 g 0.08 mmol) was introduced into a 50 mL
round flask, containing a mixture of 4-hydroxybenzaldehyde
(0.625 mmol, 76.3 mg) and benzaldehyde (1.875 mmol, 0.19
mL) dissolved in glacial acetic acid/nitrobenzene mixture (7
mL/5 mL). Then, pyrrole (2.5 mmol, 0.17 mL) was added and
the temperature was settled at 120 °C along 2 hours. The hot
suspension was filtered and the resulting solid material
washed with tetrahydrofuran (THF). To induce precipitation, n-
hexane (ca. 50 mL) was added. The Erlenmeyer flask
containing the statistical porphyrin mixture was left overnight
in the refrigerator and the solid was collected by filtration and
purified by column chromatography using silica gel as
stationary phase, using n-hexane:CH2Cl2 (1:3) as eluent to
collect the first fraction (5,10,15,20-tetraphenyl porphyrin) and
then with CH2Cl2 to collect the second fraction. This was
(4)
To porphyrin
3 (40 mg, 0.05 mmol) dissolved in 5 mL of CH3CN
a solution of TBAF (0.15mL, 0.25mmol) in THF was added. The
reaction mixture was left for 30minutes at 100ºC. The
resultant product was purified by silica gel column
chromatography using CH2Cl2 as eluent, giving the pure
porphyrin as an amorphous violet solid (m.p. > 300 ºC), in 82%
yield.
UV-vis (toluene): λmax, nm (ε, M-1∙cm-1) 420 (3.6x105), 514
(2.3x104), 545 (6.1x103), 591 (6.9x103), 656 (4.4x103). 1H NMR
(400 MHz, CDCl3): δ, ppm 8.84 (s l, 8H, β-H), 8.22 (d, J=6.4Hz,
6H, Ar-H), 8.13 (d, J=8.4Hz, 2H, Ar-H), 7.78-7.73 (m, 9H, Ar-H),
7.30 (d, J=8.4Hz, 2H, Ar-H), 5.01-4.88 (m, 2H, -CH2-), 4.55-4.46
(m, 2H, -CH2-), -2.77 (s, 2H, NH). 19F RMN (376.5 MHz, CDCl3):
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δ, ppm: -222.56 (s, 1F). HRMS-ESI-TOF [M+H]+.m/z 677.2721;
Notes and references
calcd.[C46H34FN4O]: 677.2638.
4.3. Radiosynthesis
No-carrier-added aqueous [18F]fluoride was produced in a
cyclotron by 18 MeV proton bombardment of 97%-enriched
18O-water via the 18O(p,n)18F nuclear reaction. In an automated
synthesis module [18F]fluoride produced (0.8–1.0 GBq) was
retained on a ion–exchange column (Sep-Pak Accell Plus QMA
from Waters) and then eluted with an acetonitrile solution of
Kryptofix® 2.2.2/K2CO3. Water was then removed
azeotropically with CH3CN under a stream of N2. To the vial
with radioactive mixture, 2 mg of porphyrin (3) was added,
previously dissolved in CH3CN, and the reaction left with
stirring at 100 ºC for 25 minutes.
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Acknowledgements
The authors thank FCT-Portugal and FEDER-COMPETE
Programme for funding PEst-OE/QUI/UI0313/2014 and
UID/QUI/00313/2013. NMR data was collected at the UC-NMR
facility, supported by REEQ/481/QUI/2006, RECI/QEQ-
QFI/0168/2012 and CENTRO-07-CT62-FEDER-002012. A.V.C.
Simões, S.M.A. Pinto and M.J.F. Calvete thanks
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SFRH/BD/65699/2009,
SFRH/BPD/84619/2012
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,
SFRH/BPD/99698/2014, respectively, all supported by FCT-
Portugal.
6 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C5RA16103G
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DOI: 10.1039/C5RA16103G
Graphical Abstract
Synopsis
Development, labeling optimization and biodistribution studies of a new [18F]
radiolabeled meso-tetraphenylporphyrin, which was prepared in a radiochemical purity
>95%. The data regarding the uptake into human bladder tumor cells and the radiotracer
biodistribution after C57BL/6 mice injection is also presented, and maximum cellular
uptake was registered after 45 min.