Craig C. Williams

Rhenium-186 hydroxyethylidene diphosphonate for the treatment of painful osseous metastases

Rhenium-186 (tin)hydroxyethylidene diphosphonate (HEDP) is a new radiopharmaceutical that localizes in skeletal metastases in patients with advanced cancer. A single intravenous administration of approximately 34 mCi (1,258 MBq) resulted in significant improvement in pain in 33 of 43 evaluable patients (77%) following the initial injection, and in 7 of 14 evaluable patients (50%) following a second treatment. Patients responding to treatment experienced an average decrease in pain of about 60%, with one in five treatments resulting in a complete resolution of pain. The only adverse clinical reaction was the occurrence after about 10% of the administered doses of a mild, transient increase in pain within a few days following injection. Statistically significant but clinically unimportant decreases in total white blood cell counts and total platelet counts were observed within the first 8 weeks following the injection; no other toxicity was apparent. Rhenium-186(Sn)HEDP is a useful new compound for the palliation of painful skeletal metastases.

Preparation of “no-carrier-added” technetium-99m complexes: Determination of the total technetium content of generator eluents

Abstract The total concentration of pertechnetate in 99 Mo/ 99m Tc generator eluents can be readily determined by ion exchange HPLC with u.v. detection. Tracking of a 7450 mCi generator through its useful clinical life leads to values of [TcO 4 − ] in the range 10 −7 −10 −6 M, and values of the ratio (moles total technetium)/(mCi 99m Tc) in the range (3−35) × 10 −12 mol/mCi. Trace amounts (ca. 0.01%) of non-pertechnetate, 99m Tc-containing impurities are detected, and generators of one manufacturer yield eluents with a large number of u.v. absorbing impurities. The total concentration of pertechnetate in generator eluents is important in determining whether or not chemistry developed with macroscopic concentrations of 99 Tc “carrier” can be translated to the “no-carrier-added” 99m Tc level. Success or failure of this translation could depend on whether the reaction controlling product formation is first- or second-order in technetium concentration.

Myocardial perfusion imaging with 99mTc-DMPE in man

Technetium-99m DMPE (99mTc-DMPE) is a newly synthesized myocardial perfusion imaging agent that shows intense myocardial accumulation in the dog. In the present study, dosimetry and potential clinical usefulness of this agent were assessed in four human subjects. Absorbed radiation doses were low, with the highest doses consisting of 200 mrad/mCi (54 μGy/MBq) to the gallbladder and 160 mrad/mCi (43 μGy/MBq) to the liver. No evidence of clinical toxicity was found. Technetium-99m DMPE did image the myocardium, but the ratio of target to nontarget activity was less favorable than that observed in the dog. Intense hepatic 99mTc-DMPE activity interfered with clinical imaging of the cardiac apex in two of the four subjects. We conclude that the prototype radiopharmaceutical, 99mTc-DMPE, is capable of myocardial perfusion imaging in man but the planar myocardial images produced are of inferior quality compared with 201Tl myocardial images. Further work is justified to develop related compounds to overcome the clinical limitations described.

Myocardial scintigraphy with 99mTc-tris-DMPE in man

Cardiac scintigraphy was performed in six patients with a documented previous myocardial infarction, in one patient with mitral regurgitation, and in four healthy volunteers following administration of 99mTc-tris-DMPE. An intense early blood pool phase permitted gated blood pool scintigraphy and left ventricular ejection fraction calculation. A myocardial phase 12–14 h later permitted myocardial perfusion imaging. The rest myocardial perfusion image quality with 99mTc-tris-DMPE appeared to be superior to the resting image quality obtained with 99mTc-dichloro-DMPE but was inferior to the resting image quality obtained with 201Tl.

Production and Application of 123I-Labeled M-Iodobenzylguanidine (123I-MIBG)

131I-Labeled m-iodobenzylguanidine (131I-mIBG) was first synthesized by Wieland and co-workers1 and soon became widely used for diagnosis of neural crest tumors, such as pheochromocytoma2 and neuroblastoma.3 Because of I-123’s superior physical properties for scintigraphic imaging compared to I-131,4 123I-mIBG has become the preferred agent for diagnosis, staging, and clinical follow-up of patients with these tumors. In addition, 123I-mIBG has shown potential for cardiac applications, such as determination of regional myocardial adrenergic activity following myocardial infarctions5 and prioritization of candidates for heart transplantation.6

Use of Syringe Shields in Clinical Practice

The syringe shield has been available for years but only recently has its use been made mandatory. This study investigates whether use of existing syringe shields in clinical practice would significantly reduce the radiation exposure to laboratory personnel. TLDs were worn on fingers of each hand by the radiopharmacist during preparation and by the physician during injection of 8–10 doses of 15–25 mCi 99mTc for brain scintigraphy. The results showed that physician hand exposure is reduced from 20–80% from the use of syringe shields but the pharmacist exposure reduction is about 50% maximum. The latter results primarily from the additional time required to read the volume accurately through the lead glass window. None of the physicians found the syringe shields to be a problem to the injection procedure, and if the patient experienced any added discomfort, it was not observable. Two conclusions are that syringe shields should be used for injecting high specific activity99mTc, and that the 1 cc shields currently on the market are unsatisfactory for nuclear medicine use.

Iofetamine hydrochloride I 123: a new radiopharmaceutical for cerebral perfusion imaging.

Iofetamine hydrochloride I 123 permits cerebral blood perfusion imaging with single photon emission computed tomography (SPECT). SPECT is more widely available than positron emission tomography, and complements anatomic visualization with X-ray computed tomography (CT) or magnetic resonance imaging. Iofetamine is an amphetamine analog that is rapidly taken up by the lungs, then redistributed principally to the liver and brain. The precise mechanism of localization has not been determined, but is believed to result from nonspecific receptor binding. Brain uptake peaks at 30 minutes postinjection and remains relatively constant through 60 minutes. The drug is metabolized and excreted in the urine, with negligible activity remaining at 48 hours. When compared with CT in stroke patients, visualization may be performed sooner after symptom onset and a larger zone of involvement may be evident with iofetamine. Localization of seizure foci and diagnosis of Alzheimers disease may also be possible. As CT has revolutionized noninvasive imaging of brain anatomy, SPECT with iofetamine permits routine cerebral blood flow imaging.