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MCHM3001 · From Molecules to Therapeutics

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Chapter 12 of 13 · MCHM3001

Radiopharmaceuticals: PET & SPECT Imaging

Lectures 19–20 of MCHM3001 cover molecular imaging agents: the positron-emitting (PET) and gamma-emitting (SPECT) isotopes, their half-lives, and the radiochemistry that installs them — including the [18F]FDG synthesis and stannyl radioiodination. The examinable skills are matching isotopes to their applications and half-lives and doing radioactive-decay calculations. It appears in Test 2 and the final.

In this chapter

What this chapter covers

  • 01Molecular imaging: a radiotracer must participate in but not perturb the biochemical process imaged
  • 02PET isotopes (positron emitters) and half-lives: C-11 20.4 min, N-13 9.96 min, O-15 2.05 min, F-18 110 min, Cu-64 12.7 h
  • 03SPECT isotopes (gamma emitters): Tc-99m 6.02 h (140 keV), I-123 13.2 h (159 keV), Tl-201, In-111, I-131
  • 04PET vs SPECT: PET is more quantitative with short-lived biologically useful isotopes but needs an on-site cyclotron; SPECT isotopes last longer and are widely available
  • 05Radioactive decay: A = A₀(½)^(t/t½); the short half-lives dictate synthesis speed and transport logistics
  • 06[18F]FDG synthesis: cyclotron ¹⁸F⁻, Kryptofix K222 to solubilise fluoride, triflate displacement then deprotection; hexokinase trapping as FDG-6-phosphate
  • 07Analogue-tracer design ladder (C-11 → F-18 → I-123 → Tc-99m: increasing availability, increasing structural change)
  • 08Iodine isotopes and stannyl radioiodination; technetium chemistry (reduce TcO₄⁻ with Sn²⁺, chelate stability order)
Worked example · free

Decay of an [18F]FDG dose during handling

Q [4 marks]. An [18F]FDG dose is calibrated to 400 MBq at production. Fluorine-18 has a half-life of 110 minutes. (a) What activity remains after 110 minutes, and after 220 minutes? (b) Why does F-18's half-life make clinical distribution feasible, whereas C-11 (t½ 20.4 min) is far harder to ship? (4 marks)
  • +1Use the decay law A = A₀(½)^(t/t½). After one half-life (t = 110 min, t/t½ = 1): A = 400 × (½)¹ = 200 MBq.
  • +1After 220 min (t/t½ = 220/110 = 2): A = 400 × (½)² = 400 × 0.25 = 100 MBq.
  • +1So the dose falls to 200 MBq at 110 min and 100 MBq at 220 min — halving every 110 minutes.
  • +1Interpret the logistics: with a 110-min half-life there is enough time to synthesise, purify, quality-check and transport [18F]FDG to nearby PET centres before too much activity is lost. C-11's 20.4-min half-life means it decays several-fold in the same window, so C-11 tracers must be made and used beside the cyclotron.
(a) 200 MBq after 110 min (one half-life) and 100 MBq after 220 min (two half-lives). (b) F-18's 110-min half-life leaves usable activity through synthesis, QC and transport to nearby sites, whereas C-11 at 20.4 min decays too fast to ship and must be used on-site.
Sia tip — For whole-number multiples of the half-life, just halve repeatedly (400 → 200 → 100) rather than reaching for exponentials. Match each isotope to its half-life and application — the exam loves 'why F-18 and not C-11'. Ask Sia to give you a decay time that is not a whole half-life so you practise the (½)^(t/t½) form.
Glossary

Key terms

PET isotope
A positron-emitting radionuclide (e.g. C-11 20.4 min, F-18 110 min, O-15 2.05 min) used for quantitative positron-emission tomography; typically short-lived and requiring an on-site or nearby cyclotron.
SPECT isotope
A gamma-emitting radionuclide (e.g. Tc-99m 6.02 h at 140 keV, I-123 13.2 h) used for single-photon emission computed tomography; longer half-lives make these more widely available than PET isotopes.
Radioactive-decay law
A = A₀(½)^(t/t½): activity halves every half-life; it sets how quickly a tracer must be synthesised, delivered and used.
[18F]FDG
2-[18F]fluoro-2-deoxyglucose, the workhorse PET tracer; made by nucleophilic fluorination (Kryptofix K222 solubilises the fluoride) and trapped in cells as FDG-6-phosphate by hexokinase without further metabolism.
Kryptofix K222
A cryptand added with base to carry 'naked' ¹⁸F⁻ into organic solvent for nucleophilic fluorination in the [18F]FDG synthesis.
Analogue-tracer ladder
The design progression C-11 → F-18 → I-123 → Tc-99m, trading increasing isotope availability against increasing structural change from the native substrate.
FAQ

Radiopharmaceuticals: PET & SPECT Imaging FAQ

How do you calculate how much of a radiotracer is left after some time?

Use A = A₀(½)^(t/t½), where A₀ is the starting activity, t½ the half-life and t the elapsed time. For whole-number multiples of the half-life you can just halve repeatedly: a 400 MBq F-18 dose (t½ 110 min) is 200 MBq after 110 min and 100 MBq after 220 min. For other times, compute the exponent t/t½ and raise one-half to that power.

What is the difference between PET and SPECT isotopes?

PET isotopes are positron emitters (C-11, N-13, O-15, F-18) that give quantitative images and can label biologically native atoms, but they are short-lived and usually need a nearby cyclotron. SPECT isotopes are gamma emitters (Tc-99m, I-123, Tl-201, In-111) with longer half-lives, so they are cheaper and available worldwide from generators, at the cost of less quantitative imaging. F-18 (110 min) sits at a sweet spot that makes PET distribution practical.

Why is F-18 so widely used when other PET isotopes exist?

Its 110-minute half-life is the key. That is long enough to synthesise, purify, quality-check and transport a tracer like [18F]FDG to PET centres a reasonable distance from the cyclotron, yet short enough to limit patient radiation dose. Isotopes like C-11 (20.4 min) or O-15 (2.05 min) decay too fast to ship, so they must be produced and used at the imaging site.

Can AI help me with the PET and SPECT material in MCHM3001?

Yes. Sia can drill isotope half-lives and their applications, work through radioactive-decay calculations, and walk through the [18F]FDG synthesis and its hexokinase trapping. It explains the radiochemistry and checks your arithmetic; it does not do graded assessment for you, and University of Sydney academic-integrity rules apply.

Study strategy

Exam move

Learn the isotope table cold — PET (C-11, N-13, O-15, F-18) and SPECT (Tc-99m, I-123) with their half-lives — because half-recall of these numbers is where marks leak. Practise the decay law A = A₀(½)^(t/t½), first with whole half-lives (just halve repeatedly) and then with awkward times, and always be ready to justify an isotope choice from its half-life (the classic 'why F-18 not C-11'). Keep the [18F]FDG synthesis as a short mechanism story (naked fluoride via K222, triflate displacement, deprotection, hexokinase trapping). When the isotope numbers slip, ask Sia to flash-quiz you and set fresh decay problems.

Working through Radiopharmaceuticals: PET & SPECT Imaging in MCHM3001? Sia is AskSia’s AI Chemistry tutor — ask any MCHM3001 Radiopharmaceuticals: PET & SPECT Imaging question and get a clear, step-by-step explanation grounded in how MCHM3001 is taught and assessed. Read this chapter free, then take your hardest questions to Sia.

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