Normal & Altered Biodistribution
Interpreting any study starts from the tracer’s expected normal biodistribution — and recognising when it is altered by technique, drugs, physiology or pathology. Free ⁹⁹ᵐTc-pertechnetate from poor labelling, injection-site problems, drug effects and organ dysfunction are common, correctable sources of error.
Each radiopharmaceutical has a characteristic normal pattern (for example, bone tracers in the kidneys and bladder; FDG in brain, myocardium, bowel and muscle; MIBG in salivary glands, liver and bowel). Deviations are either a clue to disease or an artefact to be recognised.
Why it matters
- The normal pattern is the reference against which every abnormality is judged.
- Many “lesions” are actually physiological or technical variants.
- Recognising altered biodistribution prevents both false positives and false negatives.
Common causes of altered biodistribution
- Free ⁹⁹ᵐTc-pertechnetate (poor labelling) → thyroid, salivary glands, stomach and bloodpool activity.
- Injection-site extravasation or lymphatic uptake mimicking or masking disease.
- Recent radiopharmaceuticals, contrast or therapy.
- Drug effects (e.g. on MIBG, DAT or bone-tracer uptake) and organ (renal/hepatic) dysfunction.
- Prior surgery, recent transfusion, or a full bladder distorting distribution.
Tracer-specific normals (examples)
- Bone (⁹⁹ᵐTc-MDP): symmetric skeletal uptake with renal/bladder excretion; growth plates active in children.
- FDG: brain, myocardium (variable), liver, bowel, urinary tract, and muscle/brown fat if not suppressed.
- MIBG: salivary glands, myocardium, liver, bowel and bladder.
- DOTATATE: spleen, kidneys, liver, adrenals, pituitary, thyroid and (variably) the pancreatic uncinate process, with urinary excretion.
Pitfalls
- Do not mistake physiological uptake for disease — know the normal map.
- Confirm adequate labelling/quality control when distribution looks “off”.
- Correlate with the CT component and clinical context.
Evidence & guidelines
- Procedure guidelines stress quality control and recognition of altered biodistribution.
- A normal-variant atlas is invaluable for training and reporting.
In depth
- Free pertechnetate contaminating a ⁹⁹ᵐTc-MDP preparation localises to the stomach, thyroid and salivary glands, mimicking soft-tissue uptake.
- Colloidal technetium species, from reduced-hydrolysed technetium in a poorly prepared kit or from aluminium contamination, are taken up by the liver and spleen.
- Aluminium overload (historically in dialysis patients) causes low-turnover osteomalacia with reduced skeletal uptake and increased hepatic and renal activity, distinguishing it from high-turnover osteitis fibrosa; moderate aluminium loading alone does not suppress uptake.
- Chronic iron overload (transfusions, haemochromatosis) reduces skeletal uptake with increased renal and soft-tissue activity; iron injections also cause uptake at intramuscular sites. The mechanism is uncertain.
- Bone-modifying drugs can diffusely reduce skeletal uptake; etidronate (a non-nitrogen-containing bisphosphonate) is the classic example, but other bisphosphonates, denosumab and drugs that impair osteoblasts (such as cabozantinib) are also listed.
- Earlier nuclear medicine studies can confound a bone scan: residual ⁹⁹ᵐTc activity (6-h half-life) is usually negligible after about a day, whereas higher-energy nuclides such as ¹³¹I (8-day half-life, 364 keV), ⁶⁷Ga and ¹¹¹In persist for days to weeks and cause septal penetration.
- Diphosphonates are cleared from plasma by skeletal uptake competing with renal excretion (about 50–60% of the dose is in bone by 3–4 h). In a superscan, avid skeletal uptake leaves little tracer for the kidneys, which appear faint or absent.
- Prior sestamibi studies can leave bowel or colonic activity, and prior sulfur-colloid studies can leave liver and spleen activity, on a later bone scan.
- IV iodinated contrast given between MDP injection and imaging is associated with intestinal, often colonic, activity on the bone scan.
Sources: EANM bone scintigraphy guideline 2016 (PMID 27262701 · labelling efficiency >95%) · SNMMI/ACNM GI bleeding procedure standard 3.0 (free pertechnetate pattern) · EANM bone scintigraphy guideline 2016 (PMID 27262701): aluminium causes diffuse hepatic uptake · EANM bone scintigraphy guideline 2016 (PMID 27262701) · PMID 3915957 (Drüeke 1985) · PMID 2510081 (Worth 1989) · PMID 6264545 (Choy, Radiology 1981)
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