1. 6321 Pharmacy Practice Management
Answers:
Introduction
Abnormal or uncontrollable growth of cells in any part of the body is regarded as cancer.
Paraganglioma is a type of abnormal cell growth seen in nerves outside the adrenal gland
near certain blood vessels. When this paraganglioma is formed in the adrenal gland is
termed as phaechromocytomas, a hormone-secreting benign tumor that occurs in the
adrenal gland; these glands are present on the top of the kidneys. This noncancerous
tumour is generally developed on one adrenal gland, but in cases, it is developed on both
the adrenal glands (nih national cancer institute, 2022). The tumor releases hormones that
elevate blood pressure and can cause headaches, and in some cases, it shows symptoms of a
panic attack in the patient. People of the age bracket of 20-50 years are usually affected by
this disease, and if the paraganglioma is cancerous, it can spread to the various parts of the
body (nih national cancer institute, 2022). This paper will discuss the latest
radiopharmaceutical therapies and procedures for treating paraganglioma and
pheochromocytomas.
Latest Radiopharmaceutical Therapies
Pheochromocytoma and paraganglioma are generally arising from the sympathetic tissue
called chromaffin tissues. There are different treatments like surgery, radiotherapy,
chemotherapy, and targeted therapy for patients with pheochromocytoma and
paraganglioma. The radiopharmaceutica radiolabeled meta-iodobenzylguanidine (mibg)
and somatostatin receptors are used for imaging or theranostic agents to treat metastatic
pheochromocytoma and paraganglioma (carrasquillo et al., 2021). 131i-mibg and 177 lu-
dotatate are types of radiation therapy used to treat metastatic pheochromocytoma and
paraganglioma. 131i-mibg therapy has been used for neuroendocrine tumors for the past
many years. Now, the u.s. Food and drug administration also approved using this high
specific activity in the treatment of metastatic pheochromocytoma and paraganglioma.
Another receptor known as radionuclide therapy 90 y- or 177 lu-dotatate is also suggested
for metastatic pheochromocytoma and paraganglioma by national comprehensive cancer
network (carrasquillo et al. 2021).
2. 131i-Mibg
131i-mibg has been one of the most promising therapies used for neuroblastoma or
metastatic pheochromocytoma and paraganglioma for many years. I-mibg stands for i-
meta-iodo-benzyl guanidine, one of the most important therapeutic agents that allow
imaging and dosimetry. Meta-iodo-benzyl guanidine is a derivative of guanethidine and a
substrate for the norepinephrine transporter. For preparing low specific activity 131i-mibg,
mibg molecule is labeled with active 131i. It was seen in preclinical studies that the
competitive uptake of 131i-mibg reduces therapeutic efficacy. The mass of mibg has some
pharmacological effects due to its competitive inhibitor property that reuptake
catecholamine (carrasquillo et al., 2021). The high specific activity 131i-mibg was one of the
first radiopharmaceuticals that were approved by the u.s. Food and drug administration to
treat metastatic pheochromocytoma and paraganglioma. It reduces the risk of the infusion
reaction and enhances the therapeutic ratio even though it has not been proven yet. It has
been described that there is almost heterogeneous progression-free survival ranging from 4
to 36 months in therapeutic trials. Low –specific-activity i-131mibg has been commercially
available in the united states and other countries of europe for the imaging of
neuroendocrine tumors since the year 1990. A study suggested that large numbers of mibg
molecules are not radiolabeled. Another drawback of using a high dose of conventional
commercial i-131 mibg is that unlabeled mibg competes for net binding sites. It lowers the
uptake of therapeutically active i-131-labelled mibg and disrupts the reuptake mechanism
of norepinephrine, which cause significant cardiovascular side effects. For imaging,
approximately 185 mci of high–specific activity i-131 mibg as dosimetry dose is given to the
patient. Data were evaluated to determine human radiation absorbed dose estimates target
lesions concerning the normal organ (noto et al., 2018). Another study (pryma et al. 2019)
suggested that high-active - specific 131i-mibg treatment offers multiple benefits, including
sustainable blood pressure control and tumour response in patients with metastatic
pheochromocytoma paraganglioma. The usual treatment or emergent effects include
nausea, myelosuppression and fatigue (pryma et al., 2019). Long-term outcomes of 125
patients with metastatic pheochromocytoma and paraganglioma treated with 131i-mibg
suggested that almost seventy-five percent of patients reported improvement in
pretreatment symptoms, including pains, fatigue, and hypertension (thorpe et al. 2020).
Another research shows that the radionuclide treatment with the use of 131-i mibg might
be helpful in the treatment of the patient with an inoperative neoplasm or rare tumors like
pheochromocytoma and paraganglioma (kotecka-blicharz et al., 2018).
177 Lu-Dotatate
Another type of receptor highly expressed in neuroendocrine tumors and can be used for
imaging and therapy is somatostatin receptors. Somatostatin is a natural 14 amino acid
peptide hormone that has some regulatory effects in the endocrine system. Lu-dotatate is
one of the most effective somatostatin receptors used to treat neuroendocrine tumors
(demirci et al., 2018). Several somatostatin receptor agonists like 90 y- and 177 lu-dotatate
3. are beneficial to many patients. Still, 177 lu-dotatate is approved by the u.s. Food and drug
administration and the european medicines agency. Guidelines for molecular imaging,
addressing screening, preparation, administration radiation safety, monitoring for 177 lu-
dotatate treatments were published by the north american neuroendocrine tumor society
and society of nuclear medicine (carrasquillo et al., 2021). Somatostatin receptors are also
expressed in other parts of the body, including the gastrointestinal tracts and pancreas, as
this somatostatin rapidly degrades and regulates hormone-related symptoms and tumor
growth. The next generation of therapeutic radiopharmaceuticals uses beta-emitting
isotopes like 90 y- and 177 lu bound to those same linker and peptide combinations.
Yttrium 90 has a half-life of 2.7 days and path length of 12mm in soft tissue, whereas
lutetium-177 has a half-life of 6,7 days and a path length of 2 mm in soft tissue. Yttrium 90
has no gamma emission, and lutetium has 11% gamma emission. After the investigation in
several clinical trials, it has been found that the lutetium-177 have similar efficacy as the
yttrium 90, whereas the toxicity in lutetium 177 is lower than the yttrium 90 (mittra, 2018).
The dose of 200 mci of 177 lu-dotatate is administered every eight weeks for four cycles
during the treatment. And each treatment visit can last for approximately 4-8 hours. After
completing all the treatment cycles, diagnostic imaging evaluation should be done after one
month, three months, six months and in some patients after the 12 months. Diagnostic
imaging is done to check the treatment response in the body of the patient (shah et al.,
2018). Lu-dotatate is peptide receptor radiotherapy, one of the promising therapies for
treating neuroendocrine tumors. 177 lu-dotatate therapies were administrated as first-line
therapy that was associated with favorable outcomes and low toxicity (vyakaranam et al.,
2019). The ongoing research done on the peptide receptor radionuclide therapy with
177 lu-dotatate shows that the efficacy and survival rate are also relatively high compared
to other treatments. The research has been conducted on 1200 patients and found that it is
a favorable therapeutic option with few side effects for patients with metastatic
neuroendocrine tumors (brabander et al., 2017). Numerous retrospective and prospective
studies have shown favorable responses in symptomatic, biochemical and objective
responses during systemic radiopharmaceutical therapy. It has been found that the
hematological side effects are usually mild in 177 lu-dotatate therapies. Three months
appears to be the optimal time to determine treatment response for radiopharmaceutical
therapies of pheochromocytoma and paraganglioma. The aim of this article is to summarize
the survival outcomes of the available radiopharmaceutical therapy based on functional
imaging scans compared toxicities and risk factors across the treatments. It provides insight
or expert recommendations for metastatic pheochromocytoma and paraganglioma and how
to select between these two therapeutic options (carrasquillo, et al. 2021).
Conclusion
Thus, it can be concluded that 131i-mibg and 177 lu-dotatate are types of radiation therapy
used to treat metastatic pheochromocytoma and paraganglioma. 131i-mibg has been one of
the most promising therapies used for neuroblastoma or metastatic pheochromocytoma
4. and paraganglioma for many years. The high specific activity 131i-mibg was one of the first
radiopharmaceuticals that were approved by the u.s. Food and drug administration. 177 lu-
dotatate therapies were administrated as first-line therapy that was associated with
favorable outcomes and low toxicity. Several somatostatin receptor agonists like 90 y- and
177 lu-dotatate are beneficial to many patients. Somatostatin receptors are also expressed
in other parts of the body, including the gastrointestinal tracts and pancreas, as this
somatostatin rapidly degrades and regulates hormone-related symptoms and tumor
growth. Lu-dotatate is peptide receptor radiotherapy, one of the promising therapies for
treating neuroendocrine tumors. Numerous retrospective and prospective studies have
shown favorable responses in symptomatic, biochemical and objective responses during
systemic radiopharmaceutical therapy.
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