Well-differentiated neuroendocrine neoplasms (NEN) have an overexpression of

somatostatin receptors (SSTRs), especially the SSTR-2 subtype. Targeting of SSTRs

is advantageous from a theranostic perspective with the use of ⁶⁸Ga-labeled peptides

such as DOTANOC, DOTATATE, and DOTATOC that form theranostic pairs as

177Lu-DOTATATE and 90Y-DOTATATOC (Lamberts et al. 1990a, b; Singh et al.

2013; Prasad et al. 2016b). ⁶⁸Ga-labeled somatostatin analogs have high sensitivity

(82–97%) and specificity (80–92%) in the detection of NENs, especially of the

gastro-entero-pancreatic origin (Gabriel et al. 2007; Haug et al. 2009), and are useful

in the detection of extra-GEP NENs (Parihar et al. 2018f) and non-NEN neoplasms

such as meningiomas (Parihar et al. 2020b) as well. Further, a novel agent 68Ga-

Exendin has shown to have superior imaging characteristics in the localization of

insulinomas, a type of well-differentiated NEN, with high levels of GLP-1 expres-

sion on the tumor cells (Parihar et al. 2018g).

In patients with advanced metastatic NEN, PRRT is a targeted therapy that can

provide high-dose radiation selectively at the disease sites, thereby minimizing

adverse effects from systemic toxicity. The radionuclides used in PRRT have

traditionally been 90Y or 177Lu, although alpha-emitters (such as ²²⁵Ac) have

been gaining traction recently (Sathekge et al. 2019). ¹⁷⁷Lu is less nephrotoxic

than ⁹⁰Y (maximum tissue penetration—1.1 cm, high energy pure-beta emitter)

because of the narrower range (0.2 cm) and lower energy (maximum—497 keV)

of the former. Another advantage with ¹⁷⁷Lu- is its additional gamma emissions

which facilitate obtaining a post-therapy scan highlighting the localization and

distribution of the delivered radiopharmaceutical and any potential unexpected

radiotracer

uptake

(Parihar

et

al.

2020c).

The

FDA

approval

of

177Lu-

DOTATATE-based PRRT was highly based on the evidence provided by the

NETTER-1 trial that compared outcomes among patients treated with

177Lu-

DOTATATE and maintenance octreotide versus the standard octreotide therapy

(existing standard of care). The authors showed a significant survival benefit for

the ¹⁷⁷Lu-DOTATATE arm with a progression free survival at 20 months being

65.2% versus 10.8% in the control arm (Strosberg et al. 2017).

Breast cancer is the leading cause of cancer-related death in women. The require-

ment of newer therapies is paramount in patients who have failed to respond to

chemotherapy,

hormonal

therapy,

or

external

beam

radiation.

99mTc-

diphosphonates, ²⁰¹Tl-chloride, and ^99mTc-methoxy-isobutyl isonitrile (MIBI) are

the most widely used SPECT tracers for breast imaging, whereas ¹⁸F-FDG forms the

standard PET/CT imaging modality with further additional tracers (e.g., ¹⁸F-FES,

68Ga-PSMA) being studied in specific clinical indications (Vadi et al. 2019; Ulaner

et al. 2021).

The human epidermal growth factor receptor-2 (HER2) targeting antibodies have

been utilized for the detection and characterization of HER2-positive lesions by

Baum et al. (2010) in patients with recurrent metastatic breast cancer. Another study

by Sharma et al. (2014) reported the utility of ^99mTc-DTPA-bis-methionine (DTPA-

bis-MET) in the detection of breast cancer.

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