Is PRRT right for you?

The first question: is your tumour somatostatin-receptor positive?

PRRT works by binding to somatostatin receptors (specifically SSTR2) on the surface of NET cells. The radioligand carries a beta-emitting Lu-177 atom to the tumour, where it deposits a therapeutic dose of radiation. If the tumour does not express somatostatin receptors strongly enough, the radioligand has nothing to bind to — and the therapy will not work.

Receptor status is assessed with a Ga-68 DOTATATE PET-CT scan (or Cu-64 DOTATATE where available). The scan is read using the Krenning scale, a four-point ordinal assessment of uptake intensity. Tumour uptake at or above the level of normal liver (Krenning 3 or 4) is generally considered adequate for PRRT. Uptake below this threshold (Krenning 1 or 2) typically excludes a patient from PRRT, regardless of other factors — because the targeting biology simply is not there.

Tumour type, grade, and progression

PRRT has the strongest evidence in well-differentiated, low-to-intermediate-grade NETs (Ki-67 typically below 20%). The NETTER-1 trial enrolled patients with mid-gut origin, well-differentiated tumours; subsequent real-world experience has extended PRRT to pancreatic NETs, foregut NETs, and even some higher-grade NETs (Ki-67 up to 55% in selected cases under the NETTER-2 framework), but with caveats around expected response.

Tumour behaviour also matters. PRRT is most appropriate for patients with documented disease progression on standard somatostatin analogue therapy (typically octreotide LAR or lanreotide). Asymptomatic, indolent, stable disease is generally not an indication; PRRT is held in reserve for progression. Equally, patients with rapidly progressing or poorly differentiated tumours may be better served by chemotherapy as first-line systemic therapy, with PRRT considered later.

Organ-function thresholds: kidneys and bone marrow

PRRT is well tolerated by most patients, but it does deliver radiation to two normal-tissue sites that need protection: the kidneys (which clear the radioligand) and the bone marrow. Standard eligibility criteria require:

• Adequate kidney function — typically a measured glomerular filtration rate (GFR) of at least 50 mL/min, often verified by Tc-99m DTPA or chromium-EDTA clearance rather than relying on creatinine alone. Borderline kidney function is not an absolute exclusion; in such cases, dose modification and intensified amino-acid renal protection during infusion are used to reduce kidney dose.
• Adequate bone marrow reserve — haemoglobin generally above 8 g/dL, platelets above 75 × 10⁹/L, and absolute neutrophil count above 1.0 × 10⁹/L. Previous extensive cytotoxic chemotherapy or external-beam radiotherapy that has compromised marrow function is taken seriously, as PRRT can deepen cytopenia and the recovery may be slow.

Liver function is also assessed, particularly in patients with significant hepatic tumour burden, but liver criteria are usually less restrictive than the renal and haematological criteria above.

Performance status and life expectancy

A patient's overall fitness matters. PRRT involves four cycles delivered roughly eight weeks apart, with active monitoring between cycles — a six-to-nine-month commitment. Standard eligibility looks for a performance status that supports completion of the full course: Karnofsky 60 or above, or ECOG 2 or below. A reasonable estimated life expectancy (typically at least six months, ideally longer) is also taken into account, because PRRT's benefit is measured in years of disease control and that benefit requires time to materialise.

That said, exceptional individual cases can warrant PRRT even where formal criteria are borderline. The decision is always individualised — a tumour board reviews the totality of the picture.

When PRRT is not the right choice

Even with positive receptor expression and adequate organ function, PRRT may not be the right next step. Common reasons to defer or decline PRRT include:

• The tumour is asymptomatic, stable, and slow-growing — somatostatin analogue therapy alone may continue to provide good control.
• The tumour is high-grade (poorly differentiated neuroendocrine carcinoma) — platinum-based chemotherapy typically takes priority, with PRRT reserved for later lines.
• The patient has uncontrolled comorbidities — uncontrolled congestive heart failure, severe COPD, active infection, or an unstable medical condition that would make the four-cycle commitment unsafe.
• Pregnancy or breastfeeding — absolute contraindications.
• The patient prefers a different approach after full informed-consent discussion.

The decision is collaborative

At FMRI, no patient is started on PRRT on the basis of a referring physician's request alone. Every potential candidate goes through a structured assessment: review of the DOTATATE PET-CT, baseline kidney function quantification, recent bloodwork, performance-status evaluation, and an honest conversation about expected outcomes, side effects, and the alternative options for each individual situation. We will, equally, decline to offer PRRT where the assessment shows it is not the right choice — even where the patient and family are keen to proceed. The right answer for one patient is rarely the right answer for the next.

If you or a loved one is considering PRRT, the most useful preparation is to bring recent imaging (especially the DOTATATE PET-CT if one has been performed), a complete medication list, the most recent kidney function and full blood count results, and a brief written summary of treatments already received. With that on the table, an individualised eligibility assessment is possible in a single consultation.