Safety and efficacy of multiple-dose versus single-dose MIBG therapy in patients with refractory pheochromocytoma and paraganglioma: a single-center retrospective analysis.

OBJECTIVE: To investigate the incidence of adverse events (AEs) following single and multiple administrations of I-131 metaiodobenzylguanidine (MIBG) therapy for inoperable pheochromocytomas and paragangliomas (PPGLs). METHODS: A single-center retrospective study was conducted on patients with inoperable PPGLs who underwent I-131 MIBG therapy between January 2000 and December 2020. A total of 28 patients with available electronic medical records were included. The treatment consisted of a single intravenous administration of 150 mCi (5.55 GBq) of I-131 MIBG. We evaluated the first MIBG treatment and repeated MIBG treatments performed within 200 days of the previous treatment. AEs for each treatment were evaluated using CTCAE version 4.0, and the statistical analysis was conducted at a significance level of p < 0.05. Objective response based on RECIST 1.1 criteria and biochemical response based on urinary catecholamines were assessed. RESULTS: The study included a total of 63 administrations, consisting of 28 single administrations (SAs), including the first administration for all 28 cases, and 35 multiple administrations (MAs), which included the second or later administrations. Hematological AEs were evaluable for 23 SAs and 29 MAs. Grade 3 or higher leukopenia occurred in 9.8% of all administrations, and Grade 3 or higher lymphopenia in 23.5%; both were manageable through observation. There were no significant differences in clinical AE Grades 1-2 (p = 0.32), hematological AE Grades 1-2 (p = 0.22), or hematological AE Grades 3-4 (p = 0.12) between MAs and SAs. Statistical analysis for each type of AE revealed significant increases in leukopenia (p < 0.01) and lymphopenia (p = 0.04). No significant difference in anemia, thrombocytopenia, or neutropenia was observed between MAs and SAs. There was no significant increase in the incidence rate of Grade 3 or higher hematological AEs for any of the parameters. The objective response rate was 0% for SAs and 36% for MAs. Biochemical response rates were 18% for SAs and 67% for MAs. CONCLUSION: In I-131 MIBG therapy for PPGLs, multiple administrations significantly increased only Grade 1 or 2 lymphopenia and leukopenia compared to single administration.

High-Specific-Activity 131 I-MIBG for the Treatment of Advanced Pheochromocytoma and Paraganglioma.

PATIENTS AND METHODS: The primary endpoints were objective response rate (ORR) and disease control rate (DCR). Secondary endpoints were duration of response, blood pressure control, safety, overall and progression-free survival rates, MIBG uptake, and correlations with genetic background. RESULTS: The study included 25 patients. Twenty-four patients had distant metastases, 17 (68%) had hormonally active tumors, and 13 (52%) had previously received antineoplastic treatment. In 24 evaluable patients, the ORR was 38%, including 2 patients with complete response, and the DCR was 83%; median time to response was 12.5 months (95% confidence interval, 4.6-25.1). Twelve patients had sporadic disease, among whom the ORR was 25% and DCR was 83%. Twelve patients had hereditary disease ( SDHB , VHL , RET ); among these, the ORR was 50%, and DCR was 83%. Plasma metanephrines normalized in 30% of patients and improved by greater than 50% in 46%. Sixteen patients had hormonally active tumors and hypertension; in 9 (56%) of these, blood pressure normalized, leading to discontinuation of antihypertensive therapy.The most common adverse events were grades 1-2 nausea/vomiting and transient bone marrow suppression. One patient developed premature ovarian failure. Reversible grades 3-4 myelosuppression were seen in 7 patients (28%). One patient had fatal pneumonitis. CONCLUSIONS: HSA- 131 I-MIBG is associated with a high DCR in patients with MPPGL, regardless of underlying genetic mutation.

Stereotactic radiotherapy for head and neck paragangliomas: How long should we wait for treatment response?

BACKGROUND AND PURPOSE: Stereotactic radiotherapy (SRT) is an effective treatment for head & neck (H&N) paragangliomas. Nevertheless, the timeline for achieving a tumor-volume-reduction (TVR) remains unclear. MATERIALS AND METHODS: Sixty-three cases with H&N paragangliomas received definitive SRT and were evaluated retrospectively. Statistical Package for the Social Sciences (SPSS) v23.0 (IBM, Armonk, NY, USA) was used for statistics. RESULTS: Sixty-eight lesions were irradiated, with glomus jugulotympanicum being the most common location (44 %). Median tumor diameter and volume were 3 cm (range, 1-7.6 cm) and 15.4 cm3 (range,1-185 cm3), respectively. Median dose was 25 Gy (range, 12-37.5 Gy) in 5 fractions (range, 1-5 fractions). Median follow-up was 40 months (range, 3-184 months). Treatment response, evaluated at a median 4.6 months post-SRT (range: 3-11 months), revealed TVR in 26 cases (41 %). During follow-up, 13 additional cases showed TVR, resulting in an overall TVR rate of 62 %. The median duration for attaining TVR was 9 months (range, 3-36 months) after SRT, and TVR occurred ≥ 12 months in 42 % of cases. Patients without prior surgery (p = 0.03) and with a longer follow-up (p = 0.04) demonstrated a higher rate of TVR. The likelihood of TVR tends to increase as the SRT dose increases (p = 0.06). Overall local control (LC) rate was 100 %. No ≥ grade 3 acute or late toxicities were observed. CONCLUSION: While SRT demonstrates an excellent LC rate for H&N paragangliomas, it's important to note that the response to treatment may require time. TVR may last beyond the initial year of treatment in a substantial proportion of patients.

Peptide receptor radionuclide therapy with 177Lu- or 90Y-SSTR peptides in malignant pheochromocytomas (PCCs) and paragangliomas (PGLs): results from a single institutional retrospective analysis.

BACKGROUND: Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare tumors and available systemic therapies are limited. AIM: To explore the role of peptide receptor radionuclide therapy (PRRT) with Yttrium-90 (90Y) and Lutetium-177 (177Lu) peptides in pheochromocytomas (PCCs) and paragangliomas (PGLs). METHODS: We retrospectively analyzed more than 1500 patients with histologically proven neuroendocrine tumors treated with 177Lu- or 90Y-DOTA-TATE or -TOC between 1999 to 2017 at our Institute. Overall, 30 patients with confirmed malignant PCCs and PGLs matched inclusion/exclusion criteria and were considered eligible for this analysis. RESULTS: Thirty (n = 30) patients were treated: 22 with PGLs and 8 with PCCs (12 M and 18 F, median age 47 [IQR: 35-60 years]). Eighteen patients (n = 18) had head and neck PGLs, 3 patients thoracic PGLs and 1 patient abdominal PGL. Sixteen patients (53%) had locally advanced and fourteen (47%) had metastatic disease. Twenty-seven (90%) patients had disease progression at baseline. Four (13%) patients were treated with 90Y, sixteen (53%) with 177Lu and ten (33%) with 90Y + 177Lu respectively. The median total cumulative activity from treatment with 90Y- alone was 9.45 GBq (range 5.11-14.02 GBq), from 177Lu- alone was 21.9 GBq (7.55-32.12 GBq) and from the combination treatment was 4.94 GBq from 90Y- and 6.83 GBq from 177Lu- (ranges 1.04-10.1 and 2.66-20.13 GBq, respectively). Seven out of 30 (23%) patients had partial response and 19 (63%) stable disease. Median follow up was 8.9 years (IQR: 2.9-12). The 5-y and 10-y PFS was 68% (95% CI: 48-82) and 53% (95% CI: 33-69), respectively, whereas 5-y and 10-y OS was 75% (95% CI: 54-87) and 59% (95% CI: 38-75), respectively. Grade 3 or 4 acute hematological toxicity occurred in three patients, two with leucopenia and one with thrombocytopenia, respectively. CONCLUSION: PRRT with 177Lu- or 90Y-DOTA-TATE or -TOC is feasible and well tolerated in advanced PGLs and PCCs.

Tumor progression in tympanojugular paragangliomas: the role of radiotherapy and wait and scan.

INTRODUCTION: Tympanojugular paragangliomas (TJ PGLs) are rare tumors characterized by bone infiltration and erosion and a close relationship with critical structures, such as cranial nerves and internal carotid artery. For these reasons, their management represents a tough challenge. Since the fifties, radio-therapy (RT) has been proposed as an alternative treatment aimed at avoiding tumor progression. However, the indolent nature of the tumor, characterized by slow growth, is a crucial factor that needs to be considered before offering radiation. METHODS: This study aims to examine tumor progression in RT patients through a systematic review of the literature and in TJ PGL patients who underwent solely wait and scan at our department. RESULTS: The rate of tumor progression in the RT group was 8.9%, while in the wait and scan cohort was 12.9%. This data suggests the innate slow growth of PGLs. However, it is not possible to draw certain conclusions because of the wide heterogeneity of the studies. CONCLUSION: When complete surgical excision of TJ PGLs is not feasible, appropriate counseling and patient selection, including comprehensive tumor classification, should be performed before proposing RT to control tumor progression, since wait and scan may represent a reasonable option in selected cases.

The Radiosurgery Society Case-Based Discussion of the Management of Head and Neck or Skull Base Paragangliomas with Stereotactic Radiosurgery and Radiotherapy.

Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have been used for the treatment of head and neck or skull base paraganglioma for a considerable time, demonstrating promising local control rates and a favorable safety profile compared with surgical approaches. Nevertheless, the choice of treatment must be carefully tailored to each patient's preferences, tumor location, and size, as well as anticipated treatment-related morbidity. This case-based review serves as a practical and concise guide for the use of SRS and FSRT in the management of head and neck or skull base paragangliomas, providing information on the diagnosis, treatment, follow-up considerations, and potential pitfalls.

Complete Response to 177 Lu-DOTATATE PRRT in a 9-Year-Old Child With Metastatic Carotid Body Paraganglioma.

ABSTRACT: We present a case involving a 9-year-old boy diagnosed with metastatic carotid body paraganglioma. The metastases were detected in cervical lymph nodes and lungs using 68 Ga-DOTANOC PET/CT imaging. The patient received peptide receptor radionuclide therapy with 177 Lu-DOTATATE. Following 3 treatment cycles, a significant improvement was observed in the metastatic lesions. After 4 cycles, the patient achieved a complete response, with a cumulative administered activity of 16.65 GBq during the therapy. This case underscores the effectiveness of using 177 Lu-DOTATATE in managing metastatic carotid body paraganglioma, offering promising results in terms of tumor regression and overall therapeutic response.

Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single-institution experience and review of the literature.

INTRODUCTION: Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature. METHODS: A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed. RESULTS: A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL. CONCLUSION: This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.

Functional Imaging Evidence of Tumor Response to High-Specific-Activity 131 I-MIBG Therapy in an 84-Year-Old Patient With Metastatic Pheochromocytoma/Paraganglioma.

ABSTRACT: An 84-year-old man with history of metastatic pheochromocytoma/paraganglioma (mPPGL) received surgery 13 years ago, with recent biopsy-proven mPPGL in the T11. 123 I-MIBG scan showed MIBG-avid liver and osseous. Given his medical condition and body habitus (weight, 45 kg; height, 140 cm), the patient was treated with high-specific-activity 131 I-MIBG (Azedra) 300 mCi ×2. He tolerated the medication and was totally asymptomatic. Series 123 I-MIBG scan showed good responses till 22 months after the first treatment at the last visit. This is probably the oldest and smallest adult mPPGL patient treated with Azedra and with prolonged good response.

Recent Advances in Radiopharmaceutical Theranostics of Pheochromocytoma and Paraganglioma.

As a rare kind of non-epithelial neuroendocrine neoplasms, paragangliomas (PGLs) exhibit various clinical characteristics with excessive catecholamine secretion and have been a research focus in recent years. Although several modalities are available nowadays, radiopharmaceuticals play an integral role in the management of PGLs. Theranostics utilises radiopharmaceuticals for diagnostic and therapeutic intentions by aiming at a specific target in tumour and has been considered a possible means in diagnosis, staging, monitoring and treatment planning. Numerous radiopharmaceuticals have been developed over the past decades. 123/131-Metaiodobenzylguanidine (123/131I-MIBG), the theranostics pair target on norepinephrine transporter system, has remained a fantastic protocol for patients with PGLs because of disease control with limited toxicity. The high-specific-activity 131I-MIBG was authorised by the Food and Drug Administration as a systemic treatment method for metastatic PGLs in 2018. Afterward, peptide receptor radionuclide therapy, which uses radiolabelled somatostatin (SST) analogues, has been exploited as a superior substitute. 68Ga-somatostatin analogue (SSA) PET showed significant performance in diagnosing PGLs than MIBG scintigraphy, especially in patients with head and neck PGLs or SDHx mutation. 90Y/177Lu-DOTA-SSA is highly successful and has preserved favourable safety with mounting evidence regarding objective response, disease stabilisation, symptomatic and hormonal management and quality of life preservation. Besides the ordinary beta emitters, alpha-emitters such as 211At-MABG and 225Ac-DOTATATE have been investigated intensively in recent years. However, many studies are still in the pre-clinical stage, and more research is necessary. This review summarises the developments and recent advances in radiopharmaceutical theranostics of PGLs.

Long-Term Outcomes in Head and Neck Paragangliomas Managed with Intensity-Modulated Radiotherapy.

OBJECTIVES: Head & Neck Paragangliomas have been historically relying on surgery mostly, with worsened quality of life and major sequelae. Conventional external radiation therapy seems to offer an equivalent control rate with a low toxicity profile. The aim of this study was to assess the safety and efficiency of intensity-modulated radiation therapy in Head & Neck paragangliomas. METHODS: This is a retrospective monocentric study conducted in a referral center, including all patients treated with IMRT, whether as an exclusive or post-operative treatment for a tympanic and jugular, carotid, or vagal paraganglioma. Data collection was performed through the manuscript and computerized medical files, including consultation, operative, imaging, pathological analyses, delineation, and treatment planning reports. Success was defined as the complete or partial regression or stabilization without progression, or relapse in accordance with the RECIST criteria. Acute toxicities and long-term sequelae were assessed. RESULTS: Our cohort included 39 patients included between 2011 and 2021: 18 patients treated for a TJ PG (45.9%), 11 patients for a carotid PG (28.4%), and 9 for a vagal PG (23.1%). Twenty-nine patients had IMRT as an exclusive treatment (74.4%), whereas 10 patients had a post-operative complementary treatment (25.6%). Median follow-up in our cohort was 2318 days (average = 2200 days, 237-5690, sd = 1281.9). Among 39 patients, 37 were successfully controlled with IMRT (94.8%), and the toxicity profile was low without any major toxicity. CONCLUSION: IMRT seems an ideal treatment, whether exclusive or post-operative for Head & Neck paragangliomas. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:607-614, 2023.

Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma.

The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.

Prognostic value of [18F]FDG-PET prior to [131I]MIBG treatment for pheochromocytoma and paraganglioma (PPGL).

OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are rare tumors arising from the neural crest cells that form the sympathetic and parasympathetic nervous systems. Radiotherapy with [131I]metaiodobenzylguanidine (MIBG) is recommended for unresectable PPGLs. We investigated the usefulness of the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting the prognosis of patients with unresectable PPGL(s) before receiving [131I]MIBG therapy. PATIENTS AND METHODS: We retrospectively analyzed the cases of 25 patients with unresectable PPGLs treated with [131I]MIBG at our hospital between 2001 and 2020. The MTV and TLG were measured in reference to liver accumulation. We divided the patients into two groups based on median values for the maximum standardized uptake value (SUVmax), MTV, and TLG, and evaluated between-group differences using log-rank tests. Cox proportional hazards models were used to determine whether there were significant differences in prognosis with respect to tumor type (pheochromocytoma vs. paraganglioma), site of metastasis, age, past treatment (chemotherapy, external radiation or [131I]MIBG treatment before the current [131I]MIBG treatment), urinary catecholamine, SUVmax, MTV, and TLG. RESULTS: The median follow-up time was 42 months (range 2-136 months). The median overall survival was 63 months. The overall survival (OS) was significantly shorter in the high-MTV group (log-rank test, p = 0.049) and the high-TLG group (p = 0.049), with no significant difference between the high- and low-SUVmax groups (p = 0.19). Likewise, there was no significant difference in prognosis according to pheochromocytoma or paraganglioma, metastasis location, age, or prior chemotherapy. A history of external radiation before [131I]MIBG treatment was associated with a significantly worse prognosis (hazard ration [HR] = 7.95, p = 0.0018). Urinary adrenaline and noradrenaline were not significant prognostic factors (p = 0.70, p = 0.25, respectively), but urinary dopamine did predict a worse outcome (p = 0.022). There was no increased risk of death for higher SUVmax or TLG (p = 0.63 and 0.057, respectively), but higher MTV did predict a worse outcome (HR = 7.27, p = 0.029). CONCLUSION: High MTV and high TLG were significantly associated with a poor prognosis after [131I]MIBG therapy for PPGLs. Other treatment strategies for such patients may need to be explored.

Favorable outcome in advanced pheochromocytoma and paraganglioma after hypofractionated intensity modulated radiotherapy.

PURPOSE: The purpose of this study was to review outcomes of patients with advanced/metastatic pheochromocytoma/paraganglioma (PPGL) treated at our institution with Intensity-modulated radiotherapy (IMRT), describe the treatment outcomes, and determine predictors. METHODS: A retrospective study on patients with advanced/metastatic PPGL who received IMRT at Peking Union Medical College Hospital between 2014 and 2019. A total of 14 patients with 17 lesions were included in this study. Ultra-hypofractionated radiation therapy was used for 7 lesions in 5 patients, while hypofractionated radiation therapy was used for 8 lesions in 7 patients. 2 patients got conventional fractionated radiotherapy. Patients who received external beam radiation therapy were given a median total radiation dose of 74.4/130 Gy (BED10/3) in a median of 13 fractions. RESULTS: OS at 2 years was 78% for all patients. For lesions evaluated by RECIST response, at least stable disease of the target lesion was achieved in 94% and distant progression in 28.5%, with an average time to progression of 5.2 months. Patients with locally advanced primary tumors or recurred in situ (n = 8) achieved 100% local control, and none of them got recurrence or distant metastasis after radiotherapy at last follow-up (median 29 months). Of patients with catecholamine-related syndromes (n = 12), 91% of symptomatic lesions improved following radiation therapy and a more than 50% decline in catecholamines. CONCLUSIONS: We have found hypofractionated IMRT effective as an additional therapy for patients with advanced primary tumors or recurrence in situ and not amenable to complete surgical resection.

Role of imaging test with radionuclides in the diagnosis and treatment of pheochromocytomas and paragangliomas.

Radionuclide imaging tests with [123I] Metaiodobenzylguanidine (MIBG), [18F] -fluorodeoxyglucose, [18F]-fluorodopa, or 68Ga-DOTA(0)-Tyr(3)-octreotate are useful for the diagnosis, staging and follow-up of pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs). In addition to their ability to detect and localize the disease, they allow a better molecular characterization of the tumours, which is useful for planning targeted therapy with iodine-131 (131I) -labelled MIBG or with peptide receptor radionuclide therapy (PRRT) with [177Lu]-labelled DOTATATE or other related agents in patients with metastatic disease. In this review we detail the main characteristics of the radiopharmaceuticals used in the functional study of PPGLs and the role of nuclear medicine tests for initial evaluation, staging, selection of patients for targeted molecular therapy, and radiation therapy planning. It also offers a series of practical recommendations regarding the functional imaging according to the different clinical and genetic scenarios in which PPGLs occur, and on the indications and efficacy of therapy with [131I]-MIBG and 177Lu-DOTATATE.

Response to targeted radionuclide therapy with [131I]MIBG AND [177Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review.

Purpose: Targeted radionuclide therapy (TRT) with [131I]MIBG and [177Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [131I]MIBG and [177Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location. Methods: This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student's t distribution. Results: In linear regression models, [131I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [131I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample. Conclusion: Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [131I]MIBG and PRRT-Lu.

I-131 metaiodobenzylguanidine therapy is a significant treatment option for pheochromocytoma and paraganglioma.

AIM: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours of chromaffin cells. Several modalities are currently available to treat patients with PPGL. These treatment modalities include surgery, chemotherapy, molecular targeted therapy and radiopharmaceuticals. METHODS: I-131 metaiodobenzylguanidine (mIBG), a classic radiopharmaceutical, can be taken up through specific receptors and sited into many, but not all, PPGL cells. RESULTS: Many studies have investigated the efficacy and toxicity of I-131 mIBG therapy. These studies reported significant results in terms of objective, hormonal and symptomatic responses as well as tolerable toxicities in patients. CONCLUSION: This article reviews the reported experiences of patients who underwent I-131 mIBG therapy for PPGL with a focus on functions and deficiencies of the therapy.