The triazene derivative of 15-(p-aminophenyl)pentadecanoic acid, 1-[4-(15-oxopentadecanoyl)phenyl]-3,3-(1,5-pentanediyl)triazene, has been sythesized as a new substrate which is readily converted to 15-(p-iodophenyl)-pentadecanoic acid (IPP). Iodine-123-labeled IPP is prepared in 30% yield in less than 30 min by reaction of the triazene with no-carrier added H123I, obtained by decay of123Xe. This rapid, regiospecific synthesis represents as improved method for the preparation of [123I]IPP.
Fatty acid are the major energy source for the myocardium, thus radiolabeled fatty have often employed as heart imaging agent to localize ischemia and as potential probes of myocardial metabolism. This paper presents the synthesis of phenyl-pentadecanoic acid (PPA) by alkylation reaction and Wollf-Kishner method. Finally, PPA was iodinated with thallium trifluoroacetate on localizing para-position of phenyl ring and radioiodine was exchanged. The overall chemical yield was 20%, labelling yield 95%, radiochemical purity 98%. Tissues distribution of mice shows that IPPA was very high activity in mice heart muscle. Autoradiogram of mouse section at 2 min is clear.
For experimental studies by animal PET [11C]-labeled 15-(4-methylphenyl)pentadecanoic acid (MePPA) is an attractive alternative to the radioiodinated 15-(4-iodophenyl)pentadecanoic
acid (IPPA) which has widely been used for imaging of fatty acid metabolism. The important physiological aspect is that the
iodine atom and the methyl substituent have similar steric and lipophilic properties. For preparation of [11C]MePPA, Stille cross-coupling reaction was applied since the same tin precursor as for the radiosynthesis of IPPA and readily
available [11C]CH3I can be used. Unsaturated tris(dibenzylideneacetone)dipalladium(0)/tri(o-tolyl)phosphine [Pd2(dba)3/P(o-tolyl)3] was taken as the catalytic system. The reaction conditions were optimized with respect to temperature, time, solvent and
amount of precursor. The best radiochemical yields of 73 ± 2.8% (decay corr.) were obtained using 0.525 mg tin precursor in
DMF at 80 °C already after a reaction time of 10 min. The labeled methyl ester was hydrolyzed by 1 M NaOH/EtOH at 80 °C within 3 min to give [11C]IPPA in a RCY of 62 ± 3.0%. The radiochemical purity of the product assured by HPLC was >99% and the overall preparation
time including HPLC purification and formulation was 40 min.
In an ongoing effort to obtain quantitative, rapid kit type labelling of [123I] radiopharmaceuticals, we have examined organomercury precursors of [123I] 15-(para-iodophenyl)-pentadecanoic acid (IPPA). Chloromercuri derivatives of phenyl pentadecanoic acid (PPA) and the PPA ethyl ester were obtained by mercuration utilizing mercuric trifluoroacetate in trifluoroacetic acid followed by treatment with acetic acid and hydrochloric acid. The most simple compound, chloromercuri PPA, proved insoluble at room temperature in the common solvents useful for radioiodination and purification. The study was extended in a systematic way to chloromercuri PPA ethyl ester and the acetoxy mercuri PPA ethyl ester. As expected, these two compounds posessed successively more useful ranges of solvent compatibility. Iodination and [123I] radioiodination were carried out with the three compounds of PPA. Chloromercuri PPA was dissolved with difficulty in acetic acid at 70°C and 71% radiochemical yield of [123I] IPPA was obtained during the course of a 5 minute reaction utilizing chloramine T. The chloromercuri PPA ethyl ester was dissolved in ethyl acetate/acetic acid (2/1 v/v) at room temperature and 87% radiochemical yield of [123I] IPPA was obtained following 10 minutes reaction. With the acetoxy mercuri PPA ethyl ester it was possible to conduct the radioiodination in ethanol again using chloramine T. A modest radiochemical yield (r. y.) (51%) of [123I] IPPA ethyl ester was obtained after 60 min. It was possible to enhance the radiochemical yield in the presence of lithium acetate (84% r. y.). The isomeric purity of the [123I] IPPA ethyl ester was unexpectedly high (99.9% para) when the radioiodination was conducted at room temperature.
Radioiodinated ω-phenylfatty acids were recently proposed as radiopharmaceuticals for determining myocardial metabolic alterations.
Therefore uptake and elimination of different radiohalogenated phenylfatty acids were determined in blood and heart muscle
of mice. The structure activity dependence i.e. the effect of length of the carbon chain, position of the substituent at the
benzene ring and type of radiohalogen was studied. Highest myocardial accumulation was found in case of a phenylfatty acid
with 15 carbon atoms in the alkylgroup and the radiohalogen attached to the benzene ring in the para position. No difference
was observed between the radiobrominated and radioiodinated substrates. In contrast to aliphatic radioiodinated fatty acids,
the radioactivity in the stomach remained almost constant (i.e. below 1% dose/organ). Thus 15-(123I-phenyl)-pentadecanoic acid (IPPA) could be brought into clinical application with success. Blood clearance and urine excretion
of the radioactivity were determined and the results found to agree with the expectations based on the principal metabolic
path of phenylfatty acids.
A rapid method for the preparation of the radioiodinated 15-(4-iodophenyl)pentadecanoic acid (p-IPPA) was developed. 131I-p-IPPA was obtained from the corresponding tin precursor and 131I-iodide using Chloramine-T as an oxidant in a radiochemical yield of 90 ± 1.4% with a radiochemical purity > 99% when performing
the labeling at room temperature within a reaction time of 3 min. The study of dependences on temperature (0, 20 and 80 °C)
and reaction time (1, 3, 5, 10 and 30 min) showed no yield increase with higher temperatures and prolonged reaction times
but the formation of side products.
The diagnosis of the myocardial diseases with 17123I-heptadecanoic acid and recently 15-(p-123I-phenyl)-pentadeconoic acid has been applied successfully. A high labeling yield and short reaction time is desired for routine
applications. The over-all yield of the complete procedure is the most important consideration. Different labeling approaches
were evaluated to increase the yield of the entrire procedure. So each laboratory is able to select the method appropriate
for their individual demands and possibilities.
The characteristics of the eutectic points and of the miscibility gaps are submitted for binary systems composed of margaric, palmitic or pentadecanoic acid as one component and succinic, glutaric or adipic acid as the other.
A simple approach is presented whereby omega halogenated fatty acids can be obtained from macrocyclic musk lactones which are industrially available. While providing a secure source of 16-iodo-hexadecanoic acid and 17-iodo-heptadecanoic acid, the scheme allows ready access to a large number of untried fatty acid analogs. Examples presented are 16-iodo-hexadecanoic acid. 16-iodo-7-hexadecenoic acid. 16-iodo-12-oxa-hexadecanoic acid, 15-iodo-pentadecanoic acid, and 15-iodo-12-keto-pentadecanoic acid.