[en] The installation and commissioning of the BARC Medical Cyclotron Facility (MCF), in October 2002, was a landmark event for very important reasons. It was the first cyclotron in the country for producing short-lived positron emitting isotopes for positron emission tomography (PET) - a nuclear medicine investigation procedure - with proven use in oncology, cardiology and neurology. The nuclear medicine fraternity in the country was eagerly awaiting to use this modality for the benefit of cancer patients in the country; and within a short time it removed the apprehensions of the nuclear medicine centres about the economic viability of investing in such high cost equipment. (author)

[en] The utility of [¹⁸F]Fluoroestradiol ([¹⁸F]FES), a fluorinated steroidal tracer for determining the tissue estrogen receptor level of breast cancer patients is clinically proven. This radiotracer is thus used in prior prediction of the response of antiestrogen therapy of primary, recurrent or metastatic breast cancer. A fully-automated, high-yield synthesis procedure is the key requirement for its availability in large scale, ensuring its wide-spread clinical use. The radiosynthesis of [¹⁸F]FES is carried out starting from MMSE (3-methoxymethyl-16α, 17β-epiestriol- Ocyclic sulfone) precursor. The low yield of [¹⁸F]FES obtained from this precursor is attributed to difficulties in the hydrolysis and purification steps after the first step radiofluoriation. Herein, we report an improved fully automated and optimized radiosynthesis procedure of ¹⁸F-16-α- Fluoroestradiol ([¹⁸F]FES) from MMSE precursor, involving hydrolysis with 2N HCl and subsequent purification using SepPak® Plus ALOX-N cartridge. The method is reliable, with considerably improved yield of the product with acceptable radiochemical purity.

[en] Overexpression of COX-2 receptors is observed in a variety of tumours. Therefore, development of suitable ¹⁸F-labelled PET radiotracers of selective COX-2 inhibitors is an attractive option to target selective and specific inhibitors of COX-2. The binding free energy [ΔG(-KCal/mole)] of Ac- etaminophen and F-18 labelled derivative of Acetaminophen has been calculated by using AUTODOCK 4.2 and crosschecked using www.swissdock.ch against the PDB code 3LN1 and has been found to be comparable in both cases. This encouraging result provides the necessary impetus towards the development of F-18 labelled derivative of Acetaminophen based on its property of selective COX-2 inhibition in designing PET radiopharmaceutical for tumour imaging. Herein, we report the fully automated radiosynthesis of the novel F-18 Fluoroethylated paracetamol by direct radio-fluoroethylation of paracetamol and subsequent purification with SEP-PAK® cartridge purification. The evaluation of the PET radiotracer has been carried out by PET/CT imaging, bio-distribution in mice tumour model and histopathological studies. The fully automated radiosynthesis of ¹⁸F-Fluoroethylated paracetamol using general purpose synthesis module which, in principle, is similar to GE TRACERlab FXFDG, has been carried out in three steps: (i) Radiosynthesis of the fluoroethylating agent, [¹⁸F]Fluoroethyl tosylate (ii) Coupling of [¹⁸F]Fluoroethyl tosylate with paracetamol in DMSO solvent and (iii) purification by SPE using Sep Pak® Plus ALOX N cartridges. Pharmacokinetic studies were evaluated by PET/CT imaging study in healthy rabbit at two different time points. Biodistribution study was carried out in nude mice bearing tumour (MDA-MB-231). COX-2 overexpression in tumours was confirmed by histopathological studies. The non-decay corrected radiochemical yield is around (25±3) % (n = 3) within 60±2 mins (total synthesis time). The radiochemical purity is >95 % as confirmed by radio-TLC and radio-HPLC coupled with UV (λ=276 nm). Biodistribution study demonstrated significant tumour accumulation and retention over a period of two hours post injection. COX-2 overexpression in tumour was confirmed by histopathological studies using mouse anti- COX2 antibody. One-hour post injection PET/CT imaging study in healthy rabbit showed very fast clearance from liver and blood, however, with high accumulation of the tracer in highly proliferating regions like bone marrow and sub-mandibular jaws. The thick leg joints showed significant uptake which can be attributed to age related inflammation in aged rabbit and the well-known fact that COX-2 is overexpressed in inflammation. Both the kidneys as well as urinary bladder showed very high tracer accumulation indicating clearance via renal route. The PET/CT image of two-hours post injection showed complete blood clearance with elimination via renal route, however with bone marrow accumulation. No bone uptake other than the thick joints was observed throughout the period of PET/CT study confirming in vivo stability of the tracer. Thick joint uptake can be attributed to age-related inflammation of the aged rabbit and the well-known fact that COX-2 is overexpressed in inflammation. F-18 labelled Paracetamol has successfully been designed, developed and evaluated as a PET tracer for tumour imaging agent based on COX-2 overexpression in a variety of tumours.

[en] A novel hypoxia trace, 1-(2-(1"8"F) Fluoroethyl)-2-Nitroimidazole was developed in our lab. The accumulation of this tracer in the hypoxic region of B16F10 melanoma tumor (C57BL6 mice) section by pimonidazole based immunohistochemistry as well as autoradiography. This methodology will be useful in the assessment of newly developed. (author)

[en] A fully automated radiosynthesis procedure of ("1"8F)Fluoroacetate by solid phase extraction purification was developed with a non-decay corrected radiochemical yield of 47.2 ± 3.0 % (n = 5) within a total synthesis time of 40 ± 1 min. Bio-distribution study in tumour (PC3: Human Prostate Cancer Cell Line) bearing nude mice showed good accumulation and retention of the tracer up to 180 min post injections. The localization of ("1"8F)Fluoroacetate in prostate tumour was further validated by autoradiography and histopathology. (author)

[en] A novel fully automated radiosynthesis procedure for [¹⁸F]Fluoromisonidazole using a simple alumina cartridge-column for purification instead of conventionally used semi-preparative HPLC was developed. [¹⁸F]FMISO was prepared via a one-pot, two-step synthesis procedure using a modified nuclear interface synthesis module. Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl) -2-O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol (NITTP) with no-carrier added [¹⁸F]fluoride followed by hydrolysis of the protecting group with 1 M HCl. Purification was carried out using a single neutral alumina cartridge-column instead of semi-preparative HPLC. The maximum overall radiochemical yield obtained was 37.49±1.68% with 10 mg NITTP (n=3, without any decay correction) and the total synthesis time was 40±1 min. The radiochemical purity was greater than 95% and the product was devoid of other chemical impurities including residual aluminum and acetonitrile. The biodistribution study in fibrosarcoma tumor model showed maximum uptake in tumor, 2 h post injection. Finally, PET/CT imaging studies in normal healthy rabbit, showed clear uptake in the organs involved in the metabolic process of MISO. No bone uptake was observed excluding the presence of free [¹⁸F]fluoride. The reported method can be easily adapted in any commercial FDG synthesis module.