Mian M. Alauddin

Background: Monoclonal antibodies (mAbs) against tumor-associated antigens have been shown to target tumors with specificity and selectivity; therefore, it was hypothesized that cancer could be treated with mAbs without side effects. In the early 1980s, clinical studies demonstrated that tumors could be visualized using radiolabeled mAbs. However, with the introduction of positron emission tomography (PET) with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), antibody-based imaging became less important because of its limited diagnostic accuracy. During the last two decades, a revival of imaging with radiolabeled mAbs has taken place, specifically PET with longer half-life isotopes. Development of immune checkpoints as targets for immunotherapy has opened opportunities for the development of a wide variety of antibodies, such as anti-CTLA-4, anti-PD-L1, and anti-PD1. Thus, imaging with these antibodies radiolabeled with 89Zr or another long–half-life PET isotope, known as immuno-PET, has become mainstream. Objective: This study aimed to review the rapid development of immuno-PET for the detection of cancer and assessment of therapeutic response combining surgery, radiation, chemotherapy, and/or immunotherapy. This review includes reports on the radiolabeling, imaging and clinical utility of ⁸⁹Zr-, ⁶⁴Cu- and ¹²⁴I-labeled mAbs. Results: More than 120 research and review articles on immuno-PET were reviewed. Conclusion: Many mAbs have been developed and used for the treatment of cancer; however, a limited number of antibodies have been radiolabeled for immuno-PET. While much progress has been made with the therapeutic applications of mAbs, immuno-PET for diagnosis and treatment assessment needs more research. Improved chelating agents and extensive imaging studies are needed to refine immuno-PET for the diagnosis of cancers and assessment of response to therapy.

Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, has emerged as a therapeutic target in solid and hematologic tumors. Although several ALK inhibitors have gained recent approval for therapy, non‐invasive indicators of target engagement or for use as predictive biomarkers in vivo are lacking. Therefore, we designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [¹⁸F]fluoroethyl‐ceritinib ([¹⁸F]‐FEC), for use with positron emission tomography. We used two methods to synthesize [¹⁸F]‐FEC. First, [¹⁸F]fluoroethyl‐tosylate was prepared, coupled with ceritinib, and the product purified to yield [¹⁸F]‐FEC. Alternatively, a precursor compound was synthesized, directly fluorinated with ¹⁸F‐fluoride, and purified to yield [¹⁸F]‐FEC. The first method produced [¹⁸F]‐FEC with an average decay‐corrected yield of 24% (n = 4), specific activity of 1200 mCi/µmol, and >99% purity; synthesis time was 115 min from the end of bombardment. The second method produced [¹⁸F]‐FEC with an average yield of 7% (n = 4), specific activity of 1500 mCi/µmol, and >99% purity; synthesis time was 65 min from the end of bombardment. The synthesis of a novel ¹⁸F‐labeled analogue of ceritinib has been achieved in acceptable yields, at high purity, and with high specific activity. The compound is a potential positron emission tomography imaging agent for the detection of ALK‐overexpressing solid tumors such as lung cancer.

Cancer is one of the leading causes of human death, and early detection can be beneficial for its timely therapy and management. For the early detection of cancer, positron emission tomography (PET) is more accurate and sensitive than other imaging modalities, such as computed tomography and magnetic resonance imaging. [¹⁸F]‐Labeled fluorodeoxyglucose is the most useful PET probe in early detection of cancer; however, its nonspecific accumulation and consequent false–positive findings warrant the identification of other PET probes. Thymidine (TdR) and its analogs have been radiolabeled for PET imaging of cellular proliferation and DNA synthesis. Because of its in vivo instability, radiolabeled TdR has not been successful in PET imaging. However, some of its radiolabeled analogs have been developed for PET imaging of cellular proliferation and DNA synthesis. In this review, the radiochemistry and production of ¹¹C‐TdR and ¹¹C/¹⁸F‐labeled TdR analogs published to date are presented. Copyright © 2013 John Wiley & Sons, Ltd.

Positron Emission Tomography (PET) is a nuclear medicine imaging technique that is widely used in early detection and treatment follow up of many diseases, including cancer. This modality requires positron-emitting isotope labeled biomolecules, which are synthesized prior to perform imaging studies. Fluorine-18 is one of the several isotopes of fluorine that is routinely used in radiolabeling of biomolecules for PET; because of its positron emitting property and favorable half-life of 109.8 min. The biologically active molecule most commonly used for PET is 2-deoxy -2-F-18-fluoro-beta-D-glucose (F-18-FDG), an analogue of glucose, for early detection of tumors. The concentrations of tracer accumulation (PET image) demonstrate the metabolic activity of tissues in terms of regional glucose metabolism and accumulation. Other tracers are also used in PET to image the tissue concentration. In this review, information on fluorination and radiofluorination reactions, radiofluorinating agents, and radiolabeling of various compounds and their application in PET imaging is presented.