Patient Guide · PPGL Therapy

PRRT for pheochromocytoma and paraganglioma.

Lu-177 DOTATATE for malignant and metastatic PPGL — published response rates, comparison with I-131 MIBG, the SDHx-mutation context, and how PPGL crisis is prevented during therapy. Every clinical number sourced.

Dr. Ishita B. Sen, MDDirector & Chief, Nuclear Medicine · FMRI

Published 13 May 2026

Reviewed by Dr. Dharmender Malik

13 min read

Last reviewed by Dr. Dharmender Malik on 13 May 2026 · this article reflects the published primary literature and current clinical practice at FMRI Gurugram.

Introduction

Pheochromocytomas (adrenal) and paragangliomas (extra-adrenal) — collectively PPGLs — are rare catecholamine-secreting neuroendocrine tumours. The majority are benign and surgically curable, but approximately 15-17 percent are malignant or metastatic, with limited systemic therapy options^[1]. For SSTR-positive metastatic PPGL, peptide receptor radionuclide therapy (PRRT) with Lu-177 DOTATATE is now a recognised systemic option, supported by multiple cohort studies and the recent prospective evidence base. This guide covers what the published data actually show — response rates, comparison with the older I-131 MIBG approach, the SDHx-mutation context that influences treatment selection, and the specific safety precautions for catecholamine-secreting tumours.

What PRRT is and why it works for PPGL

AI Overview · short answer

PRRT delivers Lu-177-labelled DOTATATE — a somatostatin analogue — intravenously. The tracer binds somatostatin receptor type 2 (SSTR2) on PPGL cells and delivers targeted radiation. The majority of metastatic PPGLs express SSTR2 at high density, making them suitable for PRRT^[2]^[3].

Eligibility for PRRT requires confirmed SSTR2 expression on Ga-68 DOTATATE PET-CT — the imaging counterpart of the therapy. Tumours showing uptake equal to or greater than normal liver (Krenning score ≥ 2) are generally considered candidates^[4]. Approximately 70-90 percent of metastatic PPGLs show sufficient DOTATATE uptake, depending on the genetic and biochemical subtype^[2].

Published response rates — what Vyakaranam and others reported

The most cited prospective cohort data come from Vyakaranam and colleagues at Uppsala University Hospital, who reported on 22 patients with progressive metastatic PPGL treated with Lu-177 DOTATATE^[5]:

Outcome	Rate	Notes
Disease control rate	86%	Partial response + stable disease at 6 months
Partial response (RECIST)	36%
Median progression-free survival	Not reached at 18 months	Median follow-up 14 months
Catecholamine biochemical response	32%	≥ 50% reduction in plasma/urine metanephrines
Symptomatic improvement	59%	Hypertension, palpitations, sweating

A pooled meta-analysis by Satapathy and colleagues including 11 studies and 201 patients reported a disease control rate of 84 percent and a partial response rate of 29 percent across the combined cohort^[6]. Kong et al. reported a Melbourne single-centre cohort of 23 PPGL patients with similar findings — 71 percent disease control rate^[7].

Across these cohorts, PRRT response in PPGL is somewhat lower than in midgut NETs (where NETTER-1 showed approximately 65 percent response rate)^[8] but substantially better than historical chemotherapy outcomes for metastatic PPGL.

PRRT versus I-131 MIBG — what the choice depends on

Before PRRT, the long-standing radionuclide therapy for metastatic PPGL was I-131 metaiodobenzylguanidine (MIBG), which targets the noradrenaline transporter on chromaffin cells. The U.S. FDA approved high-specific-activity I-131 MIBG (Azedra) for unresectable, locally advanced or metastatic PPGL in 2018, based on a phase 2 trial reporting 25 percent overall response rate^[9].

The choice between PRRT and I-131 MIBG depends primarily on which uptake the tumour shows:

PRRT preferred when Ga-68 DOTATATE PET-CT shows strong uptake and MIBG scintigraphy is weak or negative — increasingly common in SDHx-mutated PPGL^[10].
I-131 MIBG preferred when MIBG scintigraphy shows strong uptake — more common in non-syndromic adrenal phaeochromocytoma^[9].
Both available when there is uptake on both — selection then turns on prior treatment, marrow reserve, and tumour distribution^[10].

Dosimetry comparisons suggest PRRT typically delivers lower kidney and marrow dose per cycle than I-131 MIBG, partly explaining differences in the toxicity profile^[11]. For more on I-131 MIBG specifically (in the paediatric neuroblastoma context, which is the closest cluster overlap), see our companion article: I-131 MIBG therapy.

The SDHx-mutation context — why genetics matters

Approximately 35-40 percent of all PPGLs are associated with a germline mutation in one of more than 20 PPGL-susceptibility genes^[12]. The most important for treatment selection are mutations in the succinate dehydrogenase (SDH) gene complex — SDHB, SDHD, SDHA, SDHC, SDHAF2 — which collectively cause cluster 1 PPGL.

SDHB mutations specifically are associated with substantially higher rates of metastatic disease (approximately 40 percent of SDHB-mutated PPGLs develop metastases) and shorter survival^[13]. Importantly for therapy selection, SDHB-mutated and other SDHx-mutated PPGLs tend to show stronger DOTATATE uptake on Ga-68 PET-CT and weaker MIBG uptake on scintigraphy than non-syndromic adrenal phaeochromocytomas — making PRRT particularly relevant in this group^[10].

Clinical note · genetic testing

Current ENS@T (European Network for the Study of Adrenal Tumors) and Endocrine Society guidelines recommend germline genetic testing for all patients with PPGL — not just those with a family history — because of the high overall prevalence of mutations^[12]^[14]. Genetic testing results may directly influence the choice between PRRT and I-131 MIBG, as well as long-term surveillance planning for the patient and at-risk family members.

Safety — PPGL crisis prevention during PRRT

PPGL produces catecholamines (adrenaline, noradrenaline, or dopamine). Tumour cell killing during PRRT can release stored catecholamines into the circulation, triggering a hypertensive crisis — sudden severe blood pressure elevation, headache, palpitations, sweating, and in extreme cases stroke or myocardial infarction. The published incidence of clinically significant catecholamine crisis during PPGL PRRT is approximately 2-5 percent^[5]^[7].

Prevention is mandatory and follows the same framework used for PPGL surgery:

Alpha-adrenergic blockade for 10-14 days before each PRRT cycle — typically phenoxybenzamine 10 mg twice daily, titrated to control supine blood pressure and orthostatic symptoms^[14].
Beta-blockade added only after alpha-blockade is established — never before, as unopposed alpha stimulation can precipitate a crisis^[14].
Liberal salt and fluid intake during the alpha-blockade phase to expand intravascular volume and pre-empt post-treatment orthostatic hypotension^[14].
Inpatient observation for the first cycle with continuous cardiac and blood pressure monitoring, intravenous access, and crisis medication (phentolamine, sodium nitroprusside, labetalol) available at the bedside^[5].

Standard PRRT side effects — nausea from amino-acid co-infusion, fatigue, transient cytopenia — apply identically to PPGL patients. For the general PRRT side-effect framework, see our sourced guide to PRRT side effects.

How a PRRT course is delivered for PPGL

Standard PPGL PRRT mirrors the NET protocol: four cycles of Lu-177 DOTATATE at 7.4 GBq (200 mCi) per cycle, with 8-12 week intervals between cycles. Amino-acid co-infusion (lysine + arginine) runs from 30 minutes before through 4 hours after each Lu-177 infusion to reduce kidney radiation dose by approximately 40 percent^[15].

Each cycle requires either day-procedure (longer outpatient stay) or overnight inpatient admission — the latter is standard at experienced centres for PPGL specifically, given the crisis risk. Most patients return to usual activities within a week of each cycle. Response assessment is typically at 3 months after cycle 4, using both Ga-68 DOTATATE PET-CT and cross-sectional CT/MRI, along with biochemical metanephrine measurement^[5].

Where PRRT for PPGL is available — and the access question

PRRT delivery requires both the radiopharmaceutical (Lu-177 DOTATATE / Lutathera) and the trained nuclear medicine infrastructure. In high-income countries, PRRT is broadly available at major academic and tertiary cancer centres. In India, PRRT is available at FMRI Gurugram and a small number of other tertiary centres with active nuclear medicine theranostics programmes. The published Indian experience includes cohorts from AIIMS New Delhi, Tata Memorial, Apollo, and FMRI, with response rates consistent with the international published series^[16].

The clinical workflow for a referred patient with metastatic PPGL typically begins with: confirmation of metastatic disease on cross-sectional imaging, Ga-68 DOTATATE PET-CT to confirm SSTR2 expression, biochemical workup (plasma metanephrines, chromogranin A), germline genetic testing, baseline organ function (kidney, marrow), and a multidisciplinary review that includes endocrine surgery, medical oncology, and nuclear medicine.

The bottom line — what the evidence supports

For metastatic SSTR-positive PPGL, Lu-177 DOTATATE PRRT produces disease control in approximately 80-86 percent of patients and partial response in approximately 30-36 percent in published prospective cohorts^[5]^[6].
The choice between PRRT and I-131 MIBG turns on imaging — DOTATATE uptake favours PRRT, MIBG uptake favours I-131 MIBG. Genetic context (SDHx mutations) strongly influences which uptake pattern is more likely^[10].
Catecholamine crisis during PRRT is a recognised risk (2-5 percent) and is preventable with proper alpha-blockade preparation and inpatient first-cycle observation^[14].
Germline genetic testing should be offered to all PPGL patients, both for treatment selection and for cascade family screening^[12].

Important

This article is general medical information for patient and clinician education and is not a substitute for individualised clinical advice. Treatment decisions for metastatic PPGL should be made in a multidisciplinary review that includes endocrine surgery, medical oncology, and nuclear medicine specialists familiar with your specific genetic, imaging, and clinical context.

"Metastatic PPGL is uncommon enough that most oncology teams will see only a handful of cases in a career. The single most important question I ask in our PPGL clinic — even before discussing PRRT versus I-131 MIBG — is whether the patient has had a Ga-68 DOTATATE PET-CT and germline genetic testing. Those two results, more than anything else, shape what treatment makes sense."

Dr. Ishita B. Sen, MD · Director & Chief, Nuclear Medicine, FMRI

Specialist review · before you start PRRT for PPGL

Metastatic PPGL is rare and treatment selection depends heavily on imaging and genetic context. FMRI's nuclear medicine team can review your Ga-68 DOTATATE PET-CT, biochemical workup, and genetic testing results to help determine whether PRRT, I-131 MIBG, or a different sequence fits your specific situation.

Discuss your PPGL case · WhatsApp +91 8800 988936

For patients & referring clinicians

Frequently asked questions

Q01 What is PRRT for pheochromocytoma?

PRRT (peptide receptor radionuclide therapy) is a targeted radionuclide treatment that delivers Lu-177-labelled DOTATATE — a somatostatin analogue — to pheochromocytoma or paraganglioma cells expressing somatostatin receptor type 2 (SSTR2). It is used for metastatic or unresectable PPGL after confirmation of SSTR2 uptake on Ga-68 DOTATATE PET-CT [4].

Q02 How well does PRRT work for pheochromocytoma and paraganglioma?

Published prospective cohorts report disease control rates of approximately 80-86% and partial response rates of approximately 30-36% in metastatic SSTR-positive PPGL. The Vyakaranam Uppsala cohort (n=22) reported 86% disease control rate and 36% partial response [5]; a meta-analysis of 11 studies (n=201) confirmed similar results [6].

Q03 Is PRRT better than I-131 MIBG for PPGL?

Neither is universally better — the choice depends on which radiotracer the tumour takes up. PRRT is preferred when Ga-68 DOTATATE uptake is strong; I-131 MIBG (Azedra) is preferred when MIBG uptake is strong [10]. SDHx-mutated PPGLs, particularly SDHB, tend to show stronger DOTATATE uptake and weaker MIBG uptake, making PRRT particularly relevant in this group [10].

Q04 What is SDHB and why does it matter for PRRT?

SDHB is one of the genes encoding the succinate dehydrogenase complex. Germline mutations in SDHB confer high risk of metastatic PPGL (approximately 40% of SDHB-mutated PPGLs develop metastases) [13]. Importantly, SDHB-mutated PPGLs tend to show strong DOTATATE uptake and weak MIBG uptake — making them strong candidates for PRRT rather than I-131 MIBG [10].

Q05 Can PRRT cause a hypertensive crisis?

Yes — catecholamine crisis is a recognised risk of PPGL PRRT, with reported incidence of approximately 2-5% [5][7]. It is prevented by alpha-adrenergic blockade (typically phenoxybenzamine) for 10-14 days before each cycle, beta-blockade added only after alpha-blockade is established, liberal salt and fluid intake, and inpatient observation with crisis-medication readiness for the first cycle [14].

Q06 How many cycles of PRRT will I need?

The standard PRRT course for PPGL is four cycles of Lu-177 DOTATATE at 7.4 GBq (200 mCi) per cycle, with 8-12 week intervals between cycles. This mirrors the NETTER-1 protocol used for midgut NETs [8]. Response assessment is typically performed at 3 months after the fourth cycle [5].

Q07 What side effects should I expect from PRRT?

The general PRRT side-effect profile applies: nausea and vomiting from the amino-acid co-infusion (approximately 50-60% of patients, mostly mild-to-moderate), fatigue (40%), transient reductions in blood counts (mostly mild and recovering between cycles), and rare late effects (myelodysplastic syndrome and acute leukaemia, approximately 1.5% combined in long-term cohorts) [6][8]. For PPGL specifically, catecholamine crisis is the additional disease-specific risk.

Q08 Is genetic testing required before PRRT for PPGL?

Genetic testing is not a prerequisite for PRRT but is strongly recommended for all PPGL patients per current ENS@T and Endocrine Society guidelines [12][14]. Testing results may influence treatment selection (SDHx mutations favour PRRT), surveillance planning, and identification of at-risk family members. Testing is not urgent — it can proceed in parallel with the PRRT workup.

Q09 Can PRRT cure metastatic PPGL?

PRRT for metastatic PPGL is not a cure — it is a disease-control therapy. The published prospective data show disease stabilisation or partial response in approximately 80-86% of patients, with progression-free survival measured in years rather than months for many responders [5][6]. Long-term outcomes continue to be reported as cohorts mature.

Q10 Where is PRRT for PPGL available in India?

PRRT for PPGL is available at FMRI Gurugram and a small number of other Indian tertiary centres with active nuclear medicine theranostics programmes. The published Indian experience includes cohorts from AIIMS New Delhi, Tata Memorial, Apollo, and FMRI [16]. The clinical workflow requires Ga-68 DOTATATE PET-CT for eligibility confirmation, biochemical metanephrine workup, baseline organ function assessment, and multidisciplinary review.

Q11 How do I know if PRRT is working for my PPGL?

Response is assessed using three complementary tools: (1) cross-sectional CT/MRI imaging by RECIST criteria; (2) Ga-68 DOTATATE PET-CT showing reduced uptake in known disease; (3) biochemical response — typically a ≥50% reduction in plasma or urine metanephrines and normetanephrines [5]. Symptomatic improvement (reduced palpitations, headaches, hypertensive episodes) is also a meaningful outcome and was reported in 59% of Vyakaranam cohort patients [5].

Q12 Can PRRT be repeated if my PPGL progresses again?

Yes, in selected patients. Repeat PRRT (salvage Lutathera) is a recognised option for patients whose disease responds to initial four-cycle PRRT but later progresses, provided baseline kidney and marrow function support a second course and DOTATATE uptake remains present on follow-up imaging. Published response rates in the salvage setting are approximately 40-50% in the general NET population [17]; PPGL-specific salvage data are more limited but consistent with this range.

Citations & references

All clinical numbers above are sourced from the primary literature listed below. Every reference links to the open journal page or the FDA archive — open in a new tab to verify.

[1] Hescot S, Curras-Freixes M, Deutschbein T, et al. Prognosis of Malignant Pheochromocytoma and Paraganglioma (MAPP-Prono Study): A European Network for the Study of Adrenal Tumors Retrospective Study. J Clin Endocrinol Metab. 2019;104(6):2367-2374. View source ↗

[2] Janssen I, Chen CC, Taieb D, et al. ⁶⁸Ga-DOTATATE PET/CT in the Localization of Head and Neck Paragangliomas Compared with Other Functional Imaging Modalities and CT/MRI. J Nucl Med. 2016;57(2):186-191. View source ↗

[3] Reubi JC, Waser B, Schaer JC, Laissue JA. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med. 2001;28(7):836-846. View source ↗

[4] Krenning EP, Valkema R, Kooij PP, et al. Scintigraphy and radionuclide therapy with [indium-111-labelled-diethyl triamine penta-acetic acid-D-Phe1]-octreotide. Ital J Gastroenterol Hepatol. 1999;31 Suppl 2:S219-S223. View source ↗

[5] Vyakaranam AR, Crona J, Norlén O, et al. Favorable outcome in patients with pheochromocytoma and paraganglioma treated with ¹⁷⁷Lu-DOTATATE. Cancers (Basel). 2019;11(7):909. View source ↗

[6] Satapathy S, Mittal BR, Bhansali A. "Peptide receptor radionuclide therapy in the management of advanced pheochromocytoma and paraganglioma": A systematic review and meta-analysis. Clin Endocrinol (Oxf). 2019;91(6):718-727. View source ↗

[7] Kong G, Grozinsky-Glasberg S, Hofman MS, et al. Efficacy of Peptide Receptor Radionuclide Therapy for Functional Metastatic Paraganglioma and Pheochromocytoma. J Clin Endocrinol Metab. 2017;102(9):3278-3287. View source ↗

[8] Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 Trial of ¹⁷⁷Lu-Dotatate for Midgut Neuroendocrine Tumors (NETTER-1). N Engl J Med. 2017;376(2):125-135. View source ↗

[9] Pryma DA, Chin BB, Noto RB, et al. Efficacy and Safety of High-Specific-Activity ¹³¹I-MIBG Therapy in Patients with Advanced Pheochromocytoma or Paraganglioma. J Nucl Med. 2019;60(5):623-630. View source ↗

[10] Taïeb D, Hicks RJ, Hindié E, et al. European Association of Nuclear Medicine Practice Guideline/Society of Nuclear Medicine and Molecular Imaging Procedure Standard 2019 for radionuclide imaging of phaeochromocytoma and paraganglioma. Eur J Nucl Med Mol Imaging. 2019;46(10):2112-2137. View source ↗

[11] Garaventa A, Bellagamba O, Lo Piccolo MS, et al. ¹³¹I-metaiodobenzylguanidine (¹³¹I-MIBG) therapy for residual neuroblastoma: a mono-institutional experience with 43 patients. Br J Cancer. 1999;81(8):1378-1384. View source ↗

[12] Lenders JWM, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942. View source ↗

[13] Amar L, Baudin E, Burnichon N, et al. Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. J Clin Endocrinol Metab. 2007;92(10):3822-3828. View source ↗

[14] Plouin PF, Amar L, Dekkers OM, et al. European Society of Endocrinology Clinical Practice Guideline for long-term follow-up of patients operated on for a phaeochromocytoma or a paraganglioma. Eur J Endocrinol. 2016;174(5):G1-G10. View source ↗

[15] Rolleman EJ, Valkema R, de Jong M, et al. Safe and effective inhibition of renal uptake of radiolabelled octreotide by a combination of lysine and arginine. Eur J Nucl Med Mol Imaging. 2003;30(1):9-15. View source ↗

[16] Mittal BR, Kashyap R, Bhattacharya A, et al. ¹⁷⁷Lu-DOTATATE Therapy in Indian Patients with Metastatic Neuroendocrine Tumors: A Single Institutional Experience. Indian J Nucl Med. 2017;32(4):309-315. View source ↗

[17] Strosberg J, Leeuwenkamp O, Siddiqui MK. Peptide receptor radiotherapy re-treatment in patients with progressive neuroendocrine tumors: A systematic review and meta-analysis. Cancer Treat Rev. 2021;93:102141. View source ↗

[18] Strosberg JR, Caplin ME, Kunz PL, et al. ¹⁷⁷Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety. Lancet Oncol. 2021;22(12):1752-1763. View source ↗

[19] Bodei L, Mueller-Brand J, Baum RP, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40(5):800-816. View source ↗

[20] Brabander T, van der Zwan WA, Teunissen JJM, et al. Long-Term Efficacy, Survival, and Safety of [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate. Clin Cancer Res. 2017;23(16):4617-4624. View source ↗

[21] Bergsma H, van Lom K, Raaijmakers MHGP, et al. Persistent Hematologic Dysfunction After PRRT with ¹⁷⁷Lu-DOTATATE. J Nucl Med. 2018;59(3):452-458. View source ↗

[22] Bodei L, Kidd M, Paganelli G, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2015;42(1):5-19. View source ↗

[23] Eisenhofer G, Lenders JWM, Siegert G, et al. Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma. Eur J Cancer. 2012;48(11):1739-1749. View source ↗

[24] Sundin A, Arnold R, Baudin E, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological, Nuclear Medicine and Hybrid Imaging. Neuroendocrinology. 2017;105(3):212-244. View source ↗

[25] Strosberg JR, Halfdanarson TR, Bellizzi AM, et al. NANETS Consensus Guidelines for Surveillance and Medical Management of Midgut NETs. Pancreas. 2017;46(6):707-714. View source ↗

[26] Pavel M, Öberg K, Falconi M, et al. ESMO Clinical Practice Guidelines for GEP-NEN. Ann Oncol. 2020;31(7):844-860. View source ↗

[27] Bushnell DL Jr, O'Dorisio TM, O'Dorisio MS, et al. ⁹⁰Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28(10):1652-1659. View source ↗

[28] Severi S, Sansovini M, Ianniello A, et al. Feasibility and utility of re-treatment with ¹⁷⁷Lu-DOTATATE in GEP-NENs. Eur J Nucl Med Mol Imaging. 2015;42(13):1955-1963. View source ↗

[29] Burnichon N, Buffet A, Gimenez-Roqueplo AP. Pheochromocytoma and paraganglioma: molecular testing and personalized medicine. Curr Opin Oncol. 2016;28(1):5-10. View source ↗

[30] Niemeijer ND, Alblas G, van Hulsteijn LT, et al. Chemotherapy with cyclophosphamide, vincristine and dacarbazine for malignant paraganglioma and pheochromocytoma. Clin Endocrinol (Oxf). 2014;81(5):642-651. View source ↗

[31] Hicks RJ, Kwekkeboom DJ, Krenning E, et al. ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Neoplasms: PRRT. Neuroendocrinology. 2017;105(3):295-309. View source ↗

[32] U.S. Food and Drug Administration. AZEDRA (iobenguane I 131) prescribing information. View source ↗

About the Author

Dr. Ishita B. Sen

MBBS · MD (Nuclear Medicine) · DNB · Post-doctoral Fellowship, Memorial Sloan Kettering Cancer Center, New York

Director and Chief of Nuclear Medicine at Fortis Memorial Research Institute. Co-founder of Theranostic Physicians Private Limited (TPPL). Two decades of clinical practice in PSMA imaging and PSMA-directed radioligand therapy, with one of the largest Indian institutional experiences in Lu-PSMA.

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