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68Ga-Radiopharmaceuticals for PET Imaging of Infection and Inflammation

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Theranostics, Gallium-68, and Other Radionuclides

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 194))

Abstract

Infection imaging has been challenging over the past four decades, which provided an excellent playing field for researchers working in this area, and till date the quest continues to find an ideal imaging agent. Labelled leukocytes were first developed in the 1970s for imaging infection lesions such as osteomyelitis, cellulitis, diabetic foot, Crohn’s disease, inflammatory bowel disease, fever of unknown origin, etc. Subsequently labelled antibiotics such as 99mTc-labelled ciprofloxacin have emerged for directly identifying live bacterial infections. From the early 1970s through the mid-1980s, 67Ga-Citrate was the prime radionuclide for imaging of inflammation and infection of musculoskeletal origin. Although 68Ga-PET was described in 1960s for tumour imaging, recent reports described 68Ga-Citrate and 68Ga-transferrin as possible agents for PET-imaging of infection due to successful application of 67Ga-Citrate SPECT in the past, despite its limitations. It is important to establish a faster imaging method for 68Ga, as its half-life is 68 min compared to 78.3 hrs for 67Ga. Preparation of 68Ga-Citrate and 68Ga-transferrin is described, with very high yield and high radiochemical purity (RCP), which is ideally suited for routine clinical studies. Biodistribution of 68Ga-Citrate-PET images were characterised with high blood pool, high liver and bone (growth plate) uptake with low soft-tissue activity. 68Ga-Citrate or 68Ga-transferrin was able to detect infected lesions in rats within 5–10 min post injection but a focal intense uptake at the lesion (SUVmax) was visualized only at 30 min, which increased for up to 6 hrs post injection with concomitant decrease in the cardiac blood pool activity. The liver and bowel activity decreased after 90 min then stabilised. In the patient studies, infection lesions were detected within 30 min post injection of 68Ga-Citrate. Cardiac blood pool and liver activities decreased during the period of study. Interestingly, there was persistent high vascular activity in the thigh region. One of the major limitations of 67Ga-Citrate SPECT is the delayed post injection waiting time of 48 hrs, in contrast to 60 min post injection waiting with 68Ga-Citrate. The distinct difference in imaging time is intriguing, although there is no chemical difference between 67Ga-Citrate and 68Ga-Citrate, except for the radiolabel. No literature is available on early imaging times using 67Ga-SPECT. When compared 68Ga/67Ga-Citrate images at 60 min post injection in normal rats, 68Ga-PET showed better images with low background activity than 67Ga-SPECT agent. This may be due to short half-life of 68Ga (68 min), as it would have decayed one half-life at 60 min post-imaging time, compared to the SPECT agent (67Ga), which would require 76 hrs to undergo one half-life. Therefore, the visual difference in background can be attributed to the difference in the half-lives of these two agents. Similarly, uptake of 68Ga by liver, cardiac blood pool activity is much lower than 67Ga at 60 min post injection period, may be attributed to the faster decay of 68Ga than 67Ga. High background activity of 68Ga-Citrate in the thorax and upper abdomen at 60 min post-injection may interfere with detecting lesions in these regions; therefore, 68Ga-PET is more suitable for imaging lesions in the lower abdomen and the extremities. The short half-life of 68Ga (68 min) may be advantageous from low dosimetry to the patients, but disadvantageous for longer periods of study. Since 68Ga-Citrate was capable of detecting infection within 60 min, the need for imaging for longer periods may not be warranted. The functional imaging was not limited to diagnosing infection but it could be extended to surgical planning and antibiotic therapy monitoring of osteomyelitis and in distinguishing prosthetic infection from loosening of prosthesis. 18F-FDG is sensitive but has the limitation of giving false positive results in patients with bone prosthesis, even if there is no infection or mobilisation. But the available literature clearly indicated 68Ga-Citrate was positive only in cases of infection. In summary, preliminary reports suggest 68Ga-Citrate PET/CT is useful in the diagnosis of suspected bone infections with reliable sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy. Preliminary reports with 68Ga-Transferrin showed it is capable of detecting both Gram-positive Staphylococcus aureus (Staph A) and Gram-negative Proteus mirobilis. This is an incidental finding but gives an insight into the potential of this agent to detect more than one bacterial infection.

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Acknowledgments

We express sincere thanks to several authors for allowing us to reproduce figures and information from their published articles as acknowledged in the respective sections.

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Authors and Affiliations

  1. Department of Nuclear Medicine & PET, Westmead Hospital and The Children’s Hospital at Westmead, Westmead, NSW, 2145, Australia

    Vijay Kumar & Dilip K. Boddeti

  2. Department of Nuclear Medicine, The Children’s Hospital at Westmead, Sydney, NSW, Australia

    Vijay Kumar & Dilip K. Boddeti

  3. Sydney Medical School, University of Sydney, Sydney, Australia

    Vijay Kumar

Authors
  1. Vijay Kumar
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  2. Dilip K. Boddeti
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Correspondence to Vijay Kumar .

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Editors and Affiliations

  1. , THERANOSTICS Center for Molecular,, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, 99437, Germany

    Richard P. Baum

  2. Inst. Kernchemie, Universität Mainz, Fritz-Straßmann-Weg 2, Mainz, 55128, Germany

    Frank Rösch

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Kumar, V., Boddeti, D.K. (2013). 68Ga-Radiopharmaceuticals for PET Imaging of Infection and Inflammation. In: Baum, R., Rösch, F. (eds) Theranostics, Gallium-68, and Other Radionuclides. Recent Results in Cancer Research, vol 194. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-27994-2_11

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  • DOI: https://doi.org/10.1007/978-3-642-27994-2_11

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