No carrier added

Table 4. Comparison of Nucleofugacity of (CH3)3N -and NO2- Groups with No Carrier Added...

The results obtained to date are considerable and show that the chemistry of the TcN group may well be the most varied and interesting of the transition metal nitrido complexes [1,9,10]. The aim of this chapter is to provide a fairly comprehensive review of the literature up to the latter part of 1994. Additional data may be found in two conference volumes [11,12] and a recent review of Tc coordination chemistry [4]. For macroscopic studies with the long-lived "Tc (ti/2 = 2.11 x 10s years) the "Tc radionuclide is denoted simply as Tc. No carrier added studies and radiopharmaceutical applications utilizing the shortlived "mTc radionuclide (ti/2 = 6.01 hours) are denoted as "mTc. 

The biodistribution of a number of no-carrier-added (nca i.e., high specific activity) radiolanthanides (141Ce, 145Sm, 149Gd, and 167Tm) in tumor-bearing mice were examined as a function... 

C]-formaldehyde has been widely used for reductive methylation reaction but because of the marked fluctuation in the reported yields as well as impurities formed in its preparation from 11C02 the tendency has been to use 11CH3I for direct methylation. However, the recent development [99, 100] of a low temperature no-carrier-added method for preparing H11CHO, coupled to the microwave-enhanced Eschwei-ler-Clarke reaction [65-68] has led to a resurgence of interest in the use of H11CHO. 

Carrier-free radiochemical is a radionuclide that is not contaminated with a stable or radioactive nuclide of the same element. The no carrier added (NCA) designation applies to most of the elements to which the term carrier free is indicated. The specific activity of a carrier-free radioisotope can be calculated by the following formula ... 

Irradiation of enriched water (>95 %) with protons (16 MeV) is the most common method used to produce no-carrier added [ F]fluoride. Fluorine being less ubiquitous than carbon, F-radiotracers can be obtained with very high specific radioactivities (50-500 GBq pmol ). The theoretically possible... 

An electrochemical cell [93,94] was used to obtain an efficient anodic deposition of no carrier added F-fluoride solubilized in the target water. The radioisotope is electrochemically adsorbed on the anode (glassy carbon electrode) and can be easily dried. An opposite electrical field releases the radionuclide directly into a solution of a phase transfer catalyst in dipolar aprotic solvents. The nucleophilic fluorination can be performed simultaneously if the electrochemically and thermally induced desorption of radioactivity is done in the presence of the precursor. However, the yields remain poor (3 % in the electrochemical n.c.a [ F]fluorination of anisole). 

Knickmeier M, Matheja P, Wichter T, Schafers KP, Kies P, Breithardt G et al. CUnical evaluation of no-carrier-added meta-[123I]iodobenzylguanidine for myocardial scintigraphy. Eur J Nucl Med 2000 27 302-307... 

Ci/mmol (6.3 x 10" TBq/mmol), the practically achieved no-carrier-added specific radioactivity is in the region of 10 Ci/mmol (3.7 x 10 TBq/mmol). Fluoiine-18 is generally recovered from the target as [ F]fluoride anion in an aqueous solution and is then engaged in nucleophilic radiofluorinations (see Section 4.1). 

Irradiation of a mixture of neon and nitric oxide gives no-carrier-added nitrosyl [ F]fluoride (ON[ F]F) [45,67], Hydrolysis yields [ F]fluoride that was proposed for bone scanning. ON[ F]F was designed with steroid labelling in mind in which addition to a double bond should lead to an a-[ F]fluoroketone entity, but this idea was not further pursued. 

Both aliphatic and aromatic nucleophilic substitution procedures involve first pre-activation of cyclotron-produced, no-carrier-added, aqueous [ Fjfluoride. 

Single- or multi-step preparation of [ F]fluoroaryl-type molecular building blocks and some applications A large number of no-carrier-added fluorine-18-labelled aromatic key-intermediates have been synthesised, opening the way to the preparation of more complicated radiopharmaceuticals via multi-step approaches. Scheme 42 non-exhaustively lists a number of para-substituted [ F]fluorobenzene compounds indicating some of their possible chemical interconnections. It also shows some of the precursors for labelling (P1-P7) that have been used for their preparation. 

Multi-step syntheses of a radiopharmaceutical involving an aromatic nucleophilic radiofluorination An example of a multi-step radiosynthetic pathway is the no-carrier-added synthesis of 6-[ F]fluoro-L-DOPA (Scheme 45). The first step involves the preparation of 4,5-dimethoxy-2-[ F]fluorobenzaldehyde from the corresponding nitro-substituted benzaldehyde. The following steps involve its condensation with an asymmetric chiral inductor [206] followed by L-selectride reduction of the... 

As has been exemplified in this chapter, fluorinations with fluorine-18 can be classified into two categories (1) the nucleophilic reactions, which usually involve no-carrier-added [ F]fluoride of high-specific radioactivity as its Kf FIF-K complex and include substitutions in the aliphatic and the /lomoaromatic series and (2) the electrophilic reactions, which mainly use moderately low-specific radioactivity molecular [ F]fluorine, or other reagents prepared from it, such as acetyl [ F] hypofluorite, and include addition across double bonds, reactions with carbanions and especially fluorodehydrogenation and fluorodemetallation reactions. 

M.S. Berridge, C. Crouzel, D. Comar, No-carrier-added F-fluoride in organic solvents Production and labeling results, J. Label. Compds Radiopharm. 19 (1982) 1639-1640. 

A. Jordanova, J. Steinbach, B. Johannsen, Radiofluorination of electron rich aromatic compounds with no carrier added [ F]perchlorylfluoride, J. Label. Compds Radiopharm. 44 (2001) S901. 

C.Y. Shiue, J.S. Fowler, A.P. Wolf, D.W. McPherson, C.D. Arnett, L. Zecca, No-carrier-added fluorine-18 labeled N-methylspiperidol Synthesis and biodistribution in mice, J. Nucl. Med. 27 (1986) 226-234. 

F.K. Hamacher, FI.FI. Coenen, G. Stocklin, Efficient stereospecific synthesis of no-carrier-added 2-[ F]-fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution, J. Nucl. Med. 27 (1986) 235-238. 

G. Angelini, M. Speranza, A.P. Wolf, C.Y. Shiue, Nucleophilic aromatic-substitution of activated cationic groups by F-18-labeled fluoride—A useful route to no-carrier-added (nca) F-18-labeled aryl fluorides, J. Fluor. Chem. 27 (1985) 177-191. 

C. Lemaire, M. Guillaume, L. Christiaens, A.J. Palmer, R. Cantineau, A new route for the synthesis of [F-18]fluoroaromatic substituted amino-acids—No carrier added i-p-[F-18]fluorophenylalanine, Appl. Radiat. Isot. 38 (1987) 1033-1038. 

C. Lemaire, P. Damhaut, A. Plevenaux, D. Comar, Enantioselective synthesis of 6-[fluorine-18]fluoro-L-DOPA from no-carrier-added fluorine-18-fluoride, J. Nucl. Med. 35 (1994) 1996-2002. 

V.W. Pike, F. Aigbirhio, Reactions of cyclotron-produced [ F]fluoride with diarylio-donium salts—a novel single-step route to no-carrier-added f F]fluoroarenes,... 

J. Ermert, C. Hocke, T. Ludwig, R. Gail, H.H. Coenen, Comparison of pathways to the versatile synthon of no-carrier-added 1-bromo-4-[ F]fluorobenzene, J. Label. Compds Radiopharm. 47 (2004) 429-441. 

A. Horti, D.E. Redmond, R. Soufer, No-carrier-added (nca) synthesis of 6-[F-18] fluoro-L-DOPA using 3,5,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6-alpha, 8-alpha, 8-alpha-beta]-6,8-methano-2H-1,4-benzoxazin-2-one, J. Label. Compds Radiopharm. 36 (1995) 409 23. 

P. Damhaut, C. Lemaire, A. Plevenaux, C. Brihaye, L. Christiaans, D. Comar, No-carrier-added asymmetric synthesis of alpha-methyl-alpha-amino acids labeled with fluorine-18, Tetrahedron 53 (1997) 5785-5796. 

C. Lemaire, S. Gillet, S. Guillouet, A. Plenevaux, J. Aerts, A. Luxen, Highly enantioselective synthesis of no-carrier-added 6-[ F]fluoro-L-DOPA by chiral phase-transfer alkylation, Eur. J. Org. Chem. 13 (2004) 2899-2904. 

A. Knochel, O. Zwernemann, Development of a no-carrier-added method for F-18-labelling of aromatic compounds by fluorodediazonation, J. Label. Compds Radio-pharm. 38 (1996) 325-336. 

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