Nuclear Medicine After Organ Transplantation

1. Kidney transplant: the renogram

• Biopsy is the reference for graft dysfunction but is invasive; ultrasound shows anatomy but not function. ⁹⁹ᵐTc-MAG3 renography adds a non-invasive functional assessment.
• Tracer: MAG3 is preferred over DTPA because its high renal extraction gives good images even with poor function. Typical adult activity is 37–185 MBq; higher activity improves the perfusion (flow) phase.
• Acquisition: supine, camera anterior over the iliac fossa; a fast flow phase, then dynamic images for 20–30 min. Add delayed static images (up to ~2 h) if a urine leak is suspected. Diuretic is less useful early after surgery.
• Baseline scan (ideally within 24–48 h): confirms perfusion, gives the reference for every later study and has prognostic value.

Complications and their scan patterns

Numbers that help

• Hilson perfusion index: area under the iliac artery curve divided by area under the graft curve (to peak) × 100. Normal is below 150; it rises when graft perfusion falls (rejection, arterial stenosis).
• Time to peak and clearance: delayed peak and poor clearance are sensitive but non-specific signs of dysfunction (ATN, rejection, toxicity or obstruction); the trend from baseline matters more than one value.
• Measured function: MAG3 clearance (ERPF) or DTPA/⁵¹Cr-EDTA GFR quantify function; a fall from the patient's own baseline is the most useful signal.
• Infection: ⁹⁹ᵐTc-DMSA is more sensitive than ultrasound for graft pyelonephritis.

FDG PET/CT for suspected acute rejection

• Inflammatory cells in rejection take up FDG. In a validation cohort of 79 recipients (86 scans) with biopsy, a mean renal SUVmean threshold of 1.6 gave sensitivity 100% and specificity 30% (AUC 0.86).
• So a low value argues strongly against acute rejection and may avoid a biopsy; a high value is non-specific (pyelonephritis, BK nephropathy, borderline changes).

2. Liver transplant

• Complications include rejection, bile leak, anastomotic stricture or obstruction, and vascular occlusion.
• HIDA (⁹⁹ᵐTc-mebrofenin): shows hepatocyte uptake, excretion and biliary drainage in one study.

3. Heart transplant

• Endomyocardial biopsy remains the reference for rejection but is invasive and prone to sampling error.
• Graft function: radionuclide ventriculography (MUGA) gives reproducible LVEF; a fall from baseline suggests rejection, ischaemia or infection.
• Innervation: the transplanted heart is denervated, so ¹²³I-MIBG uptake is initially absent; partial sympathetic re-innervation over years can be tracked and has prognostic value.
• Acute cellular rejection: FDG uptake from inflammatory infiltrates has been described, but specificity is low and it remains investigational.
• Cardiac allograft vasculopathy (CAV): a diffuse, largely microvascular coronary disease affecting about half of recipients by 10 years. Relative SPECT perfusion can look normal when disease is uniform; PET absolute myocardial blood flow and flow reserve detect the global reduction and predict outcome.

4. Lung transplant

• V/Q scintigraphy: split lung function, suspected embolism, and surgical complications such as bronchial or arterial anastomotic stenosis.
• Chronic lung allograft dysfunction (CLAD): affects about half of recipients by 5 years; bronchiolitis obliterans syndrome is the commonest form. Small-airway obstruction causes air trapping and reflex vasoconstriction, giving matched patchy V/Q defects.
• Gastric emptying: vagal injury at surgery commonly causes gastroparesis; delayed emptying promotes reflux and micro-aspiration, a recognised risk factor for CLAD.

5. Infection and fever of unknown origin

6. Post-transplant lymphoproliferative disorder (PTLD)

• Lymphoid proliferations after solid-organ or stem-cell transplantation, linked to immunosuppression and Epstein–Barr virus.
• Risk by organ: lowest after kidney transplantation (about 1–2%), higher after heart and lung, highest after intestinal/multivisceral transplantation (up to ~20%).
• Timing: bimodal — early (first year, mostly EBV-positive) and late (often EBV-negative).
• WHO 2017 categories: non-destructive (plasmacytic hyperplasia, infectious mononucleosis-like, florid follicular hyperplasia); polymorphic; monomorphic (B-cell, most often DLBCL; T/NK-cell); classic Hodgkin lymphoma-type.
• Extranodal disease is common (gut, lung, CNS, skin, the graft itself) and can mimic infection or rejection.

Role of FDG PET/CT

• Diagnosis and staging: pooled sensitivity 89.7% and specificity 90.9% (bivariate meta-analysis, 336 recipients); FDG found lesions missed by CT/MRI in about 28% of patients.
• Response: Deauville/Lugano scoring as in lymphoma; FDG findings altered or guided treatment in about 29%. Criteria are validated for DLBCL- and Hodgkin-type disease, less so for polymorphic and non-destructive lesions.
• Pitfalls: false negatives in early lesions and high-background organs; false positives from inflammation.

7. What is coming

• CXCR4 PET (⁶⁸Ga-pentixafor): images leukocyte infiltration; in 13 kidney recipients with complicated urinary infection, PET/MRI identified allograft infection. Investigational.
• Other targets of alloimmune activation (e.g. activated T-cell markers) are being studied in animal models only.

Summary

1. Do a baseline MAG3 scan early after kidney transplantation and compare every later scan with it.
2. ATN: preserved perfusion with poor function that improves; rejection: reduced perfusion and function, usually after day 5.
3. A low renal FDG uptake argues strongly against acute rejection.
4. HIDA is good for bile leaks but can miss strictures.
5. Use PET flow reserve for heart allograft vasculopathy, V/Q for lung grafts, and FDG PET/CT for infection and PTLD.

Test yourself

5 quick questions. Pick an answer to see the explanation.

References

1. Lovinfosse P, Weekers L, Pottel H, et al. [18F]FDG PET/CT imaging disproves renal allograft acute rejection in kidney transplant recipients with acute kidney dysfunction: a validation cohort. Eur J Nucl Med Mol Imaging. 2022;49(1):331-5.
2. Kim YJ, Lee KT, Jo YC, et al. Hepatobiliary scintigraphy for detecting biliary strictures after living donor liver transplantation. World J Gastroenterol. 2011;17(21):2626-31.
3. Fishman JA. Infection in organ transplantation. Am J Transplant. 2017;17(4):856-79.
4. Erba PA, Glaudemans AWJM, Veltman NC, et al. Image acquisition and interpretation criteria for 99mTc-HMPAO-labelled white blood cell scintigraphy: results of a multicentre study. Eur J Nucl Med Mol Imaging. 2014;41(4):615-23.
5. Ballova V, Muoio B, Albano D, et al. Diagnostic performance of 18F-FDG PET or PET/CT for detection of post-transplant lymphoproliferative disorder: a systematic review and a bivariate meta-analysis. Diagnostics (Basel). 2020;10(2):101.
6. Montes de Jesus FM, Kwee TC, Nijland M, et al. Performance of advanced imaging modalities at diagnosis and treatment response evaluation of patients with post-transplant lymphoproliferative disorder: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2018;132:27-38.
7. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.
8. Derlin T, Gueler F, Bräsen JH, et al. Integrating MRI and chemokine receptor CXCR4-targeted PET for detection of leukocyte infiltration in complicated urinary tract infections after kidney transplantation. J Nucl Med. 2017;58(11):1831-7.